Study of Oral Treatments for Hepatitis C (PRIORITIZE)

• ClinicalTrials.gov Identifier: NCT02786537
• Recruitment Status: Completed
• First Posted: June 1, 2016
• Results First Posted: November 24, 2020
• Last Update Posted: December 6, 2021
• Sponsor: University of Florida
• Collaborators: Patient-Centered Outcomes Research Institute; Merck Sharp & Dohme LLC; AbbVie
• Information provided by (Responsible Party): University of Florida

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Chronic Hepatitis C
• Interventions: Drug: SOF/LDV (sofosbuvir/ledipasvir); Drug: PrOD (ombitasvir/paritaprevir/ritonavir with dasabuvir) (Phase 1 only); Drug: EBR/GZR (elbasvir/grazoprevir); Drug: Ribavirin
• Enrollment: 1275

Participant Flow

Recruitment Details

Participants were consented at 34 US centers Between June 2016 and March 2018. Patients' insurance was screened for inclusion of SOF/LDV on formulary (the HCV regimen not provided by the study). However, following randomization, participants who were unable to obtain SOF/LDV through insurance received 1 of 2 Direct Acting Antiviral (DAA) HCV Treatment regimens 1)EBR/GZR or 2)PrOD during Phase 1 and received EBR/GZR during Phase 2.

Pre-assignment Details

This study initially (Phase 1) randomized subjects to receive 1 of 3 HCV DAA regimens (EBR/GZR +/- RBV, LDV/SOF +/- RBV, or PrOD +/-RBV). In phase 2 of this study, randomization to PrOD regimen was discontinued and newly enrolled subjects were randomized to either EBR/GZR +/- RBV or LDV/SOF +/- RBV. Efficacy data was analyzed via original 'randomization' and as subjects were 'actually treated (regimen actually received)' while safety analysis was evaluated by actual treatment received.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV	PrOD/RBV(Phase 1 Only)	PrOD (Phase 1 Only)
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir) (Zepatier™) orally once daily with RBV for 12 to 16 weeks (provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food and with RBV: Ribavirin (200 mg pill) 1-3 pills/day, once or twice daily. Total daily dosage ranged from 200 to 1200 mg.	Patients received EBR/GZR (elbasvir/grazoprevir) (Zepatier™) orally once daily (without RBV) for 12 to 16 weeks EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks. Duration of treatment according to HCV treatment provider.	Patients received SOF/LDV(sofosbuvir/ledipasvir) (Harvoni®) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV/sofosbuvir/ledipasvir: Sofosbuvir/Ledipasvir (400/90 mg) 1 tablet daily for approximately 12 to 24 weeks (treatment duration is per discretion of HCV provider) RBV (200 mg pill): 1-3 pills, once or twice daily (dosing per discretion of HCV provider). Total daily dosage ranged from 200 to 1200 mg.	Patients received SOF/LDV (sofosbuvir/ledipasvir) (Harvoni®) orally once daily with or without food 12 to 24 weeks SOF/LDV: Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks (treatment duration is per discretion of HCV provider)	PrOD: Two ombitasvir/paritaprevir/ritonavir once daily and dasabuvir (Viekira) once or twice daily with a meal for 12 to 24 weeks + RBV (provider discretion). Randomization to PrOD discontinued January 2017. ombitasvir/paritaprevir/ritonavir (Phase 1 only): (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) for 12 to 24 weeks with food (treatment duration and use of ribavirin as per HCV provider) Dasabuvir: 250 mg twice daily for 12 to 24 weeks with a meal RBV: Ribavirin 200 to 600 mg once or twice daily	Randomization to Prod discontinued January 2017 (defining end of Phase 1) PrOD: Two ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily for 12 to 24 weeks ombitasvir/paritaprevir/ritonavir (Phase 1 only): (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) for 12 to 24 weeks (treatment duration as per HCV provider) Dasabuvir: 250 mg daily for 12 to 24 weeks
Period Title: As Randomized
Started	56	644	15	413	99	48
Completed	50	582	15	378	87	41
Not Completed	6	62	0	35	12	7
Reason Not Completed
Adverse Event	0	11	0	4	6	2
Lack of Efficacy	0	0	0	1	0	0
Withdrawal by Subject	1	2	0	1	1	0
Death	0	2	0	3	1	0
Non-compliance with study drug	1	11	0	1	0	1
Lost to treatment follow-up	4	32	0	24	4	4
Incarceration	0	1	0	0	0	0
Opiate Dependency Relapse	0	1	0	0	0	0
HCV drugs stolen from pt	0	1	0	0	0	0
Advised to stop after lapse in dosing	0	1	0	0	0	0
Subject lost insurance	0	0	0	1	0	0
Period Title: As Treated
Started [1]	56	664	15	394	99	47
Completed	50	602	15	359	87	40
Not Completed	6	62	0	35	12	7
Reason Not Completed
Adverse Event	0	11	0	4	6	2
Death	0	2	0	3	1	0
Lack of Efficacy	0	0	0	1	0	0
Lost to Follow-up	4	32	0	25	4	4
Non-compliance with study drug	1	11	0	1	0	1
Lost insurance	0	0	0	1	0	0
Withdrawal by Subject	1	2	0	0	1	0
Incarceration	0	1	0	0	0	0
Opiate dependency relapse	0	1	0	0	0	0
Drugs stolen from patient	0	1	0	0	0	0
Advised to stop tx after loss of meds	0	1	0	0	0	0
[1] Numbers represent treatment regimen that study participant actually started (received).

Baseline Characteristics

Arm/Group Title		EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV	PROD With RBV (Phase 1 Only)	PROD (Phase 1 Only)	Total
Arm/Group Description		Patients received EBR/GZR (elbasvir/grazoprevir) tablet tablet once daily with RBV for 12 to 16 weeks (provider discretion) EBR/GZR (Elbasvir/grazoprevir 50/100mg tablet) once daily with or without food with or without RBV for 12 to 16 weeks (with RBV)	Patients received EBR/GZR (elbasvir/grazoprevir) tablet tablet once daily without RBV for 12 to 16 weeks (provider discretion) EBR/GZR (Elbasvir/grazoprevir 50/100mg tablet): 1 tablet once daily with or without food with or without RBV for 12 to 16 weeks (without RBV)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) sofosbuvir/ledipasvir: Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks with Ribavirin (RBV) (treatment duration and use of ribavirin is per discretion of HCV provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks without ribavirin (per discretion of provider) SOF/LDV: Sofosbuvir/Ledipasvir (400/90 mg tablet ) 1 tablet orally once daily for approximately 12 to 24 weeks	Phase 1 only - Two ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily for 12 to 24 weeks +/- RBV (provider discretion) ombitasvir/paritaprevir/ritonavir (Phase 1 only): (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider) Dasabuvir: 250 mg daily for 12 to 24 weeks	Phase 1 only - Two ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily for 12 to 24 weeks ombitasvir/paritaprevir/ritonavir (Phase 1 only): (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) for 12 to 24 weeks Dasabuvir: 250 mg daily for 12 to 24 weeks	Total of all reporting groups
Overall Number of Baseline Participants		56	644	15	413	99	48	1275
Baseline Analysis Population Description		Study participants as randomized to HCV treatment
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	56 participants	644 participants	15 participants	413 participants	99 participants	48 participants	1275 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	44 78.6%	547 84.9%	8 53.3%	319 77.2%	86 86.9%	35 72.9%	1039 81.5%
	>=65 years	12 21.4%	97 15.1%	7 46.7%	94 22.8%	13 13.1%	13 27.1%	236 18.5%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	56 participants	644 participants	15 participants	413 participants	99 participants	48 participants	1275 participants
		55.1 (11.0)	53.3 (12.2)	61.1 (6.6)	56.2 (11.1)	54.5 (11.3)	59.9 (10.1)	54.7 (11.8)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	56 participants	644 participants	15 participants	413 participants	99 participants	48 participants	1275 participants
	Female	13 23.2%	280 43.5%	6 40.0%	157 38.0%	35 35.4%	16 33.3%	507 39.8%
	Male	43 76.8%	364 56.5%	9 60.0%	256 62.0%	64 64.6%	32 66.7%	768 60.2%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	56 participants	644 participants	15 participants	413 participants	99 participants	48 participants	1275 participants
	Hispanic or Latino	5 8.9%	44 6.8%	0 0.0%	26 6.3%	5 5.1%	1 2.1%	81 6.4%
	Not Hispanic or Latino	51 91.1%	586 91.0%	14 93.3%	375 90.8%	90 90.9%	45 93.8%	1161 91.1%
	Unknown or Not Reported	0 0.0%	14 2.2%	1 6.7%	12 2.9%	4 4.0%	2 4.2%	33 2.6%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	56 participants	644 participants	15 participants	413 participants	99 participants	48 participants	1275 participants
		56	644	15	413	99	48	1275
HCV RNA; Mean (Standard Deviation); Unit of measure: 10^6 units IU/mL
	Number Analyzed	56 participants	644 participants	15 participants	413 participants	99 participants	48 participants	1275 participants
		4.9 (6.7)	3.1 (4.9)	5.9 (4.7)	3.5 (4.4)	3.5 (3.8)	3.7 (4.2)	3.4 (4.7)

Outcome Measures

1. Primary Outcome

Title	Sustained Virologic Response (SVR12) mITT With Imputation-Phase 1 and 2 EBR/GZR, SOF/LDV
Description	SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation at discretion of provider). mITT with imputation (missing=failure). Total number of subjects reflects participants from EBR/GZR with or without RBV and SOF/LDV with or without RBV randomized during Phase 1 and Phase 2.
Time Frame	12 weeks post-treatment

Outcome Measure Data

Analysis Population Description

mITT with imputation, Missing SVR data = Failure. Numbers represent participants according to arm randomized (Period 1). Population excludes participants who did not start any HCV treatment.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV
Arm/Group Description:	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received EBR/GZV tablet (elbasvir/grazoprevir) once daily for 12 to 16 weeks EBR/GZV (50/100mg) tablet: once daily with or without food 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily (with or without food) for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)
Overall Number of Participants Analyzed	56	644	15	413
Measure Type: Count of Participants; Unit of Measure: Participants
	40 71.4%	516 80.1%	14 93.3%	335 81.1%

2. Primary Outcome

Title	Phase 1/2 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation)
Description	SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site). Number of subjects reflects participants who started EBR/GZR or SOF/LDV- based treatment (with or without RBV) during Phase 1 and 2.
Time Frame	12-24 weeks post HCV treatment

Outcome Measure Data

Analysis Population Description

All mITT without imputation (missing data excluded). Includes only number of participants for whom SVR12 data is available and based on study drug as randomized (Period 1). Participants for whom SVR 12 is not available are excluded from this table.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV
Arm/Group Description:	Patients received elbasvir/grazoprevir (EBR/GZR) tablet orally once daily with or without Ribavirin (RBV) for 12 to 16 weeks (provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks Ribavirin (RBV) (200 mg pill)- 1-3 pills orally once or twice daily (dosage at provider discretion)	Patients received elbasvir/grazoprevir (EBR/GZR) once daily for 12 to 16 weeks EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (treatment duration per discretion of provider) sofosbuvir/ledipasvir: 1 Sofosbuvir/Ledipasvir (400/90 mg) tablet once daily with or without food for approximately 12 to 24 weeks Ribavirin (200 mg pill): 200 to 600 mg once or twice daily (treatment duration and dosage of ribavirin as per discretion of HCV provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily for 12 to 24 weeks (treatment duration as per discretion of HCV treatment provider) SOF/LDV (400/90 MG TABLET): 1 tablet orally once daily for 12 to 24 weeks
Overall Number of Participants Analyzed	46	540	15	344
Measure Type: Count of Participants; Unit of Measure: Participants
	40 87.0%	516 95.6%	14 93.3%	335 97.4%

3. Primary Outcome

Title	Phase 1-Sustained Virologic Response (SVR12) mITT With Imputation
Description	SVR (Sustained Virologic Response) 12 will be defined as patients who have undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site). mITT with imputation (missing=failure). Total number of subjects reflects participants from Phase 1 only.
Time Frame	12 weeks post-treatment

Outcome Measure Data

Analysis Population Description

mITT with imputation, Missing SVR data =failure. Numbers represent participants according to arm randomized (period 1). Population excludes participants who did not start any HCV treatment.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV	PrOD With RBV	PrOD
Arm/Group Description:	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received EBR/GZR tablet (elbasvir/grazoprevir) once daily for 12 to 16 weeks EBR/GZR (50/100mg) tablet: 1 tablet once daily with or without food 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily (with or without food) for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV) ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily with food for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider) Dasabuvir (250 mg tablet): 1 tablet once or twice daily with food for 12 to 24 weeks (dosage at discretion of provider) RBV (200 mg tablet): 1-3 tablets once or twice daily for 12 to 24 weeks (dosage and duration at discretion of provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks (treatment duration as per HCV provider) Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks
Overall Number of Participants Analyzed	13	134	6	105	99	48
Measure Type: Count of Participants; Unit of Measure: Participants
	9 69.2%	108 80.6%	6 100.0%	88 83.8%	77 77.8%	42 87.5%

4. Primary Outcome

Title	Phase 1 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation)
Description	SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site). Number of subjects reflects participants randomized during Phase 1 only.
Time Frame	12 -24 weeks post-treatment

Outcome Measure Data

Analysis Population Description

Participants analyzed based on HCV treatment as assigned by randomization.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV	PrOD With RBV	PrOD (Phase 1 Only)
Arm/Group Description:	Patients received EBR/GZR (elbasvir/grazoprevir) tablet tablet once daily with Ribavirin (RBV) for 12 to 16 weeks (provider discretion) EBR/GZR: Elbasvir/grazoprevir (50/100mg) 1 tablet once daily with or without food with or without RBV for 12 to 16 weeks Ribavirin at dosages ranging from 200mg to 600 mg daily (or twice daily) can be added to HCV DAA treatment regimen at discretion of HCV treatment provider	Patients received EBR/GZR (elbasvir/grazoprevir) tablet tablet once daily without RBV for 12 to 16 weeks (provider discretion) EBR/GZR: 1 Elbasvir/grazoprevir (50/100mg) tablet once daily with or without food for 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) tablet orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) sofosbuvir/ledipasvir: Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider) RBV: At discretion of provider, 200 mg pill, 1-3 pills/day, 1-2 times/day (daily dosing ranging from 200mg to 1200 mg daily) added to HCV treatment regimen	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider) SOF/LDV (Sofosbuvir/Ledipasvir 400/90 mg tablet): 1 tablet daily for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider)	Patients received PrOD (ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily) for 12 to 24 weeks with Ribavirin (RBV) (use and dosage at provider discretion) ombitasvir/paritaprevir/ritonavir (Phase 1 only): (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet ) 2 tablets daily for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider) Dasabuvir: 500 mg tablet once or twice daily (morning and evening) RBV: At discretion of provider, 200 mg pill, 1-3 pills/day, 1-2 times/day (daily dosing ranging from 200mg to 1200 mg daily) added to HCV treatment regimen	Patients received ProD (ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily) for 12 to 24 weeks without Ribavirin (at provider discretion) ombitasvir/paritaprevir/ritonavir (Phase 1 only): Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider) Dasabuvir: 250 mg tablet twice daily for 12 to 24 weeks
Overall Number of Participants Analyzed	10	113	6	92	80	42
Measure Type: Count of Participants; Unit of Measure: Participants
	9 90.0%	108 95.6%	6 100.0%	88 95.7%	77 96.3%	42 100.0%

5. Primary Outcome

Title	Mean Change in Headache-PRO Scores -Phase 1
Description	Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Mean change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement in symptom.
Time Frame	Baseline to On-Treatment

Outcome Measure Data

Analysis Population Description

Analysis limited to patients who completed a baseline and on-treatment PRO and as treated (Period 2) during Phase 1 only.

Arm/Group Title	EBR/GZR With Ribavirin (RBV)	EBR/GZR Regimen	SOF/LDV With RBV	SOF/LDV	PrOD With RBV Regimen	PrOD
Arm/Group Description:	Patients received EBR/GZR (elbasvir/grazoprevir) once daily withRBV (at discretion of provider) for 12 to 16 weeks (provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg - 1 tablet once daily with or without food for 12 to 16 weeks RBV: Ribavirin (200 mg pills) 1-3 pills/day, 1-2 times/day (Total dosage 200-1200 mg day)	Patients received EBR/GZR (elbasvir/grazoprevir) once daily without RBV (at discretion of provider) for 12 to 16 weeks (provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg - 1 tablet once daily with or without food for 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with ribavirin (RBV) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) without ribavirin (RBV) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider) RBV (200 mg pill): 1-3 pills once or twice daily for 12 to 24 weeks (dosage and duration at discretion of provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). Treatment duration as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)
Overall Number of Participants Analyzed	9	84	5	61	62	28
Mean (Standard Deviation); Unit of Measure: units on a scale
	0.0 (1.4)	-0.8 (3.5)	-0.7 (5.0)	-0.5 (4.8)	-0.2 (4.7)	-2.2 (4.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SOF/LDV, PrOD
	Comments	PROD vs. SOF/LDV based regimens as reported in PRO (ALL PATIENTS WHO STARTED TREATMENT BY ARM AS TREATED), population limited to as randomization date of the last PrOD patient start date - RBV FREE REGIMENS
	Type of Statistical Test	Superiority
	Comments	Superiority test derived by comparing whether the 95% CI includes zero.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -3.6 to 0.3
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EBR/GZR Regimen, PrOD
	Comments	RBV free EBR/GZR regimen compared to PrOD in consideration that RBV usage was determined by provider and not study randomization.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; -0.4 to 3.1
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method. CI for median derived from PROC QUANTREG.

6. Primary Outcome

Title	Mean Change in Headache-EBR/GZR and SOF/LDV
Description	Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Mean change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD
Time Frame	Baseline to On-Treatment

Outcome Measure Data

Analysis Population Description

Analysis limited to participants who completed both baseline and end of treatment PRO

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV
Arm/Group Description:	Patients received EBR/GZR (elbasvir/grazoprevir) once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg to 600mg tablet): 1 to 3 tablets once or twice daily (dosage and duration per discretion of provider)	Patients received EBR/GZR (elbasvir/grazoprevir ) once daily for 12 to 16 weeks (duration of treatment per provider discretion) without Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)
Overall Number of Participants Analyzed	40	403	10	222
Mean (Standard Deviation); Unit of Measure: units on a scale
	-0.8 (3.1)	-0.7 (4.4)	0.4 (6.2)	-0.8 (5.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBR/GZR, SOF/LDV
	Comments	Analysis based on RBV free EBR/GZR regimen vs SOF/LDV (all patients who started treatment by arm as treated)
	Type of Statistical Test	Superiority
	Comments	Superiority test completed by comparing whether the 95% CI includes zero.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.6 to 1.0
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.

7. Primary Outcome

Title	Median Change in Headache -Phase 1
Description	Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Median change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD
Time Frame	12 weeks (Baseline and Average On-treatment Score)

Outcome Measure Data

Analysis Population Description

Analysis limited to patients randomized up to last patient randomized to PrOD and participants who completed baseline and on-treatment survey.

Arm/Group Title	EBR/GZR (Elbasvir/Grazoprevir) With RBV	EBR/GZR (Elbasvir/Grazoprevir)	SOF/LDV (Sofosbuvir/Ledipasvir) With RBV	SOF/LDV (Sofosbuvir/Ledipasvir)	PrOD (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir) With RBV (Phase 1 Only)	PrOD (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir)
Arm/Group Description:	Patients received 1 EBR/GZR (elbasvir/grazoprevir) (Zepatier) tablet (50/100mg) once daily for 12 to 16 weeks (provider discretion) with Ribavirin (RBV) EBR/GZR (elbasvir/grazoprevir): Elbasvir/grazoprevir (50/100mg) tablet once daily with or without food with or without RBV for 12 to 16 weeks Ribavirin: 200 mg/tablet, 1-3/day, taken 1-2 times per day (dosage at discretion of provider).	Patients received 1 EBR/GZR (elbasvir/grazoprevir) tablet (50/100 mg) once daily for 12 to 16 weeks (treatment duration per provider discretion) EBR/GZR (elbasvir/grazoprevir): Elbasvir/grazoprevir (50/100mg) tablet once daily with or without food for 12 to 16 weeks	Patients received 1 SOF/LDV (sofosbuvir/ledipasvir) (Harvoni) tablet (400/90 mg) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (duration and usage of RBV at discretion of provider). SOF/LDV (sofosbuvir/ledipasvir): Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks Ribavirin (RBV): 200 mg/tablet(capsule), 1-3 pills/day, 1-2 times/day.	Patients received 1 SOF/LDV (sofosbuvir/ledipasvir) tablet (400/90 mg) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider) SOF/LDV (sofosbuvir/ledipasvir): Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks (treatment duration at discretion of HCV provider)	Patients received Pr0D (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir) orally daily with food for 12 to 24 weeks with RBV (Ribavirin). Ombitasvir/Paritaprevir/Ritonavir (12.5/75/50 mg/tablet) -2 tablets once daily with food for 12 to 24 weeks and 1 dasabuvir tablet (250 mg) twice daily with food for 12 to 24 weeks. RBV (200 mg/pill) 1-3 pills/day, 1-2 times/day (use and dosage at provider discretion). Total daily RBV dosage ranged from 200 to 1200 mg.	Patients received 2 ombitasvir/paritaprevir/ritonavir tablets (12.5/75/50 mg) once daily and 1 dasabuvir (250 mg) tablet twice daily with food for 12 to 24 weeks without Ribavirin (as per provider instructions) PrOD (ombitasvir/paritaprevir/ritonavir with dasabuvir) (Phase 1 only): Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) (2 tablets taken orally) and Dasabuvir (250 mg tablet) (1 tablet twice daily) with food for 12 to 24 weeks (treatment duration as per HCV provider)
Overall Number of Participants Analyzed	9	84	5	61	62	28
Median (Full Range); Unit of Measure: units on a scale
	0.0; (-2.0 to 2.0)	0.0; (-12.5 to 9.5)	-2.0; (-6.5 to 5.0)	-1.0; (-12.8 to 13.5)	0.0; (-17.0 to 8.5)	-1.0; (-15.0 to 3.0)

8. Primary Outcome

Title	Median Change in Headache-Phase 2
Description	Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Median change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of median change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD
Time Frame	Baseline -on Treatment (12-16 weeks)

Outcome Measure Data

Analysis Population Description

Analysis limited to patients randomized to EBR/GZR regimen or SOF/LDV regimen and participants who completed both baseline and on treatment survey.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV
Arm/Group Description:	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV for 12 to 16 weeks. EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received EBR/GZR tablet (elbasvir/grazoprevir) once daily for 12 to 16 weeks (duration per investigator's discretion) EBR/GZR (50/100mg) tablet: 1 tablet once daily with or without food 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) without RBV SOF/LDV (400/90 mg tablet): 1 tablet once daily (with or without food) for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)
Overall Number of Participants Analyzed	40	403	10	222
Median (Full Range); Unit of Measure: units on a scale
	-1.0; (-7.0 to 6.0)	0.0; (-20.0 to 14.0)	0.5; (-9.5 to 11.5)	-0.5; (-20.0 to 14.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBR/GZR, SOF/LDV
	Comments	Analysis of EBR/GZR vs. SOF/LDV irrespective of RBV usage in consideration that RBV usage was determined by provider and not study randomization.
	Type of Statistical Test	Superiority
	Comments	Superiority test comparison based on whether the 95% CI includes zero
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; 0.0 to 1.0
	Estimation Comments	The comparisons between regimens can be viewed as superiority test, by comparing whether the 95% CI includes zero

9. Primary Outcome

Title	Mean Change in Nausea/Vomiting PRO Score -Phase 1
Description	Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement. The estimates of mean change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes. The model expressed mean score as a function of DAA regimen, cirrhosis status, HCV genotype, sex, age, race, and previous treatment status.
Time Frame	Baseline to On-Treatment

Outcome Measure Data

Analysis Population Description

Analysis is limited to patients who completed at least one baseline and one end of treatment PRO survey during Phase 1 (end date corresponds to last PrOD patient start date)

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV	PrOD With RBV	PrOD
Arm/Group Description:	Patients received EBR/GZR (elbasvir/grazoprevir ) once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg to 600mg tablet): 1 to 3 tablets once or twice daily (dosage and duration per discretion of provider)	Patients received EBR/GZR (elbasvir/grazoprevir ) once daily for 12 to 16 weeks (duration of treatment per provider discretion) without Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)
Overall Number of Participants Analyzed	8	79	5	58	59	25
Mean (Standard Deviation); Unit of Measure: units on a scale
	1.3 (5.0)	-1.4 (8.8)	-3.9 (4.0)	-0.7 (10.7)	2.5 (8.6)	0.7 (12.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SOF/LDV, PrOD
	Comments	Analysis based on RBV free SOF/LDV vs. PrOD in consideration that RBV usage was determined by provider and not study randomization and limited RBV sample size.
	Type of Statistical Test	Superiority
	Comments	Superiority test comparison based on whether the 95% CI includes zero
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; -4.2 to 7.0
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SOF/LDV, PrOD
	Comments	RBV free PrOD vs. SOF/LDV regimens (all patients who started treatment by arm as treated, population is limited to as randomization date of the last PrOD patient start date)
	Type of Statistical Test	Superiority
	Comments	Superiority test comparison based on whether the 95% CI includes zero.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; -4.2 to 7.0
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.

10. Primary Outcome

Title	Mean Change in Nausea/Vomiting PROMIS Score -EBR/GZR vs. LDV/SOF
Description	Participants completed the Patient Reported Outcomes surveys (PROs) 'PROMIS Nausea/Vomiting -4 Short Form' at baseline and during treatment. Raw scores are converted to standardized T-scores with a range of 45.0-80.1. Higher scores indicate worse nausea/vomiting. Results presented as mean difference from baseline to average of on Treatment Scores (highest/worst) score during treatment. A negative (-) PROMIS change score is suggestive of symptom improvement or lack of drug side effect. Estimates of mean change were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes.
Time Frame	Baseline and Average On-Treatment Score

Outcome Measure Data

Analysis Population Description

Patients with Baseline PROMIS Nausea/vomiting score who started treatment by arm as treated and completed baseline and on-treatment survey.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV
Arm/Group Description:	Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg tablet): 1 to 3 tablets once or twice daily (dosage and duration per discretion of provider)	Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) without Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks	Patients received 1 tablet SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dosage 200 mg- 1200 mg.	Patients received 1 tablet SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)
Overall Number of Participants Analyzed	37	381	9	202
Mean (Standard Deviation); Unit of Measure: units on a scale
	-0.3 (8.3)	-0.6 (8.7)	-1.6 (4.7)	-0.4 (9.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBR/GZR, SOF/LDV
	Comments	RBV free EBR/GZR vs. SOF/LDV (all patients who started treatment by arm as treated)
	Type of Statistical Test	Superiority
	Comments	Superiority test comparison based on whether the 95% CI includes zero
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.6 to 1.3
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.

11. Primary Outcome

Title	Median Change in Nausea PRO Score -Phase 1
Description	Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement. The estimates of change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes.
Time Frame	Baseline to end of treatment

Outcome Measure Data

Analysis Population Description

Analysis limited to patients who completed baseline and on treatment Nausea short form during Phase 1 (up to last PrOD randomized) as treated.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV	PrOD With RBV	PrOD
Arm/Group Description:	Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg tablet): 1 - 3 tablets,1-2 times per day (dosage and duration per discretion of provider)	Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider) RBV(Ribavirin) (200mg tablet): 1 - 3 tablets,1-2 times per day (dosage and duration per discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider) SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration as per discretion of HCV provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider) RBV(Ribavirin) (200mg tablet): 1 - 3 tablets,1-2 times per day (dosage and duration per discretion of provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)
Overall Number of Participants Analyzed	8	79	5	58	59	25
Median (Full Range); Unit of Measure: units on a scale
	0.4; (-6.5 to 10.0)	0.0; (-22.2 to 20.8)	-6.1; (-8.0 to 0.9)	0.0; (-21.6 to 23.7)	0.0; (-19.2 to 22.2)	0.0; (-25.2 to 31.7)

12. Primary Outcome

Title	Median Change in Nausea PROMIS Score-EBR/GZR SOF/LDV
Description	Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for change represent improvement. The estimates of change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes.
Time Frame	Baseline- On Treatment (up to 16 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV
Arm/Group Description:	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) RBV(Ribavirin) (200mg tablet): 1 - 3 tablets,1-2 times per day (dosage and duration per discretion of provider)	Patients received EBR/GZV tablet (elbasvir/grazoprevir) once daily for 12 to 16 weeks EBR/GZV (50/100mg) tablet: once daily with or without food 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: RBV(Ribavirin) (200mg tablet): 1 - 3 tablets,1-2 times per day (dosage and duration per discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily (with or without food) for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)
Overall Number of Participants Analyzed	37	381	9	202
Median (Full Range); Unit of Measure: score on a scale
	0.0; (-21.0 to 18.3)	0.0; (-29.2 to 23.3)	0.0; (-8.0 to 7.3)	0.0; (-26.1 to 24.9)

13. Primary Outcome

Title	Mean Change in Fatigue PRO Score -Phase 1
Description	Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.
Time Frame	Baseline to On-treatment

Outcome Measure Data

Analysis Population Description

Analysis limited to patients who completed baseline and at least one on-treatment Fatigue PRO survey during phase 1 as treated.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV	PrOD With RBV	PrOD
Arm/Group Description:	Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg tablet): 1 to 3 tablets, once or twice daily (dosage and duration per discretion of provider). Total daily dosage ranged from 200 to 1200 mg daily.	Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) without Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider) RBV (Ribavirin) 200mg tablet: 1 to 3 tablets, once or twice daily at discretion of provider. Total daily dosage ranged from 200 to 1200 mg.	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider) SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)	Patients received PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider) RBV (200 mg tablet): 1-3 tablets, 1-2 times per day, daily for 12 to 24 weeks (dosage and duration at discretion of provider)	Patients received PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)
Overall Number of Participants Analyzed	9	78	5	59	59	27
Mean (Standard Deviation); Unit of Measure: units on a scale
	1.5 (7.7)	-1.2 (9.2)	-7.2 (10.2)	-2.0 (7.9)	-1.9 (11.3)	-3.0 (7.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBR/GZR, PrOD
	Comments	RBV free EBR/GZR vs. PrOD regimens as reported in PRO (all patients who started treatment by arm as treated, population is limited to as randomization date of the last PrOD patient start date). Analysis limited to RBV free regimen in consideration RBV usage determined by provider and not study randomization.
	Type of Statistical Test	Superiority
	Comments	Superiority test based on whether the 95% CI includes zero
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 95%; -1.9 to 5.5
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SOF/LDV, PrOD
	Comments	RBV free SOF/LDV vs. PrOD regimens as reported in PRO (all patients who started treatment by arm as treated, population is limited to as randomization date of the last PrOD patient start date)
	Type of Statistical Test	Superiority
	Comments	Superiority test based on whether the 95% CI includes zero
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -4.6 to 2.7
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.

14. Primary Outcome

Title	Mean Change in Fatigue PRO -EBR/GZR vs SOF/LDV
Description	Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.
Time Frame	Baseline and Average On-Treatment Score

Outcome Measure Data

Analysis Population Description

Patients with Baseline PROMIS Fatigue score who started treatment by arm as treated (Period 2)

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV
Arm/Group Description:	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV (at discretion of provider) for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 - 3 tablets,1-2 times per day, daily for 12 to 16 weeks (dosage and duration per discretion of provider).	Patients received EBR/GZR (elbasvir/grazoprevir) once daily without RBV (at discretion of provider) for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion)	Patients received sofosbuvir/ledipasvir orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets, once or twice daily orally with food, daily for 12 - 24 weeks (use of RBV and dosage at discretion of provider)	Patients received sofosbuvir/ledipasvir orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)
Overall Number of Participants Analyzed	38	398	10	213
Mean (Standard Deviation); Unit of Measure: score on a scale
	-1.0 (7.7)	-2.1 (9.1)	-3.7 (8.3)	-2.2 (8.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBR/GZR, SOF/LDV
	Comments	Analysis limited to RBV free regimens in consideration that RBV usage determined by provider and not study randomization. All patients who started treatment by arm as treated.
	Type of Statistical Test	Superiority
	Comments	Superiority test comparison based on presence of zero in 95% CI.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -1.4 to 1.6
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method

15. Primary Outcome

Title	Median Change in Fatigue -Phase 1
Description	Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.
Time Frame	Baseline to End of Treatment

Outcome Measure Data

Analysis Population Description

Analysis is limited to patients who completed baseline and on-treatment fatigue PRO during Phase 1 (last PrOD patient started). Safety profiles of the evaluated regimens in PRIORITIZE are by actual treatment received.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR Regimen	SOF/LDV With RBV	SOF/LDV	PrOD Regimen With RBV	PrOD
Arm/Group Description:	Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg tablet): 1 to 3 tablets, once or twice daily (dosage and duration per discretion of provider). Total daily dosage ranged from 200 to 1200 mg daily.	Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) without Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks	Patients received sofosbuvir/ledipasvir orally once daily with or without food 12 to 24 weeks with or without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets, once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received sofosbuvir/ledipasvir orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)
Overall Number of Participants Analyzed	9	78	5	59	59	27
Median (Full Range); Unit of Measure: units on a scale
	2.2; (-9.2 to 15.0)	-0.9; (-31.0 to 24.2)	-10.2; (-20.0 to 7.2)	-3.4; (-21.1 to 16.4)	-0.2; (-33.4 to 17.8)	-4.1; (-17.5 to 16.6)

16. Primary Outcome

Title	Median Change in Fatigue-Phase 2
Description	Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.
Time Frame	Baseline-On Treatment (up to 16 weeks)

Outcome Measure Data

Analysis Population Description

Analysis limited to Period 2 -as treated, participants who completed baseline and on-treatment surveys.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV
Arm/Group Description:	Patients received elbasvir/grazoprevir (EBR/GZR) tablet orally once daily with or without Ribavirin (RBV) for 12 to 16 weeks (provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks Ribavirin (RBV) (200 mg tablet)- 1-3 tablets orally, once or twice daily (dosage at provider discretion). Total daily dosage 200 -1200 mg.	Patients received elbasvir/grazoprevir (EBR/GZR) once daily for 12 to 16 weeks EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (treatment duration per discretion of provider) sofosbuvir/ledipasvir: 1 Sofosbuvir/Ledipasvir (400/90 mg) tablet once daily with or without food for approximately 12 to 24 weeks Ribavirin (200 mg tablet): 1-3 tablets, once or twice daily (treatment duration and dosage of ribavirin as per discretion of HCV provider).	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily for 12 to 24 weeks (treatment duration as per discretion of HCV treatment provider) SOF/LDV (400/90 MG TABLET): 1 tablet orally once daily for 12 to 24 weeks
Overall Number of Participants Analyzed	38	398	10	213
Median (Full Range); Unit of Measure: units on a scale
	-1.3; (-19.1 to 15.0)	-1.2; (-31.6 to 24.2)	-2.4; (-20.0 to 7.2)	-1.4; (-39.0 to 20.7)

17. Primary Outcome

Title	Mean Change in HCV- PRO- Phase 1
Description	HCV-PRO, a survey for patients with HCV that measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess 'overall functioning and well-being'. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being. Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered.
Time Frame	Baseline to End of Treatment

Outcome Measure Data

Analysis Population Description

Analysis limited to patients who completed baseline and at least one on treatment Fatigue Short form. Evaluation is based on actual HCV regimen received.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV	PrOD With RBV	PrOD
Arm/Group Description:	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV (at discretion of provider) for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet orally once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets, once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dose ranging from 200 mg to 1200 mg.	Patients received EBR/GZR (elbasvir/grazoprevir) once daily without RBV (at discretion of provider) for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet orally once daily with or without food for 12 to 16 weeks (duration per provider discretion)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider) RBV (Ribavirin) 200mg tablet: 1 to 3 tablets, once or twice daily at discretion of provider. Total daily dosage ranged from 200 to 1200 mg.	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider) SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider) RBV (200 mg tablet): 1-3 tablets, once or twice daily for 12 to 24 weeks (dosage and duration at discretion of provider).	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). Treatment duration as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)
Overall Number of Participants Analyzed	9	84	5	61	61	29
Mean (Standard Deviation); Unit of Measure: units on a scale
	-0.9 (12.4)	5.6 (14.0)	2.5 (7.1)	6.9 (16.9)	3.2 (22.8)	9.9 (12.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBR/GZR, PrOD
	Comments	Analysis based on RBV free regimens -all patients who started treatment by arm as treated, population is limited to as randomization date of the last PrOD patient start date.
	Type of Statistical Test	Superiority
	Comments	Superiority test determined by comparing presence of zero in CI.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.3
	Confidence Interval	(2-Sided) 95%; -9.9 to 1.3
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SOF/LDV, PrOD
	Comments	RBV free regimens as reported in PRO (all patients who started treatment by arm as treated, population limited to as randomization date of the last PrOD patient start date)
	Type of Statistical Test	Superiority
	Comments	Superiority comparison by viewing presence of zero in CI.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.0
	Confidence Interval	(2-Sided) 95%; -3.4 to 9.4
	Estimation Comments	[Not Specified]

18. Primary Outcome

Title	Median Change in HCV-PRO (Overall Well Being) -Phase 1
Description	HCV-PRO, a survey for patients with HCV that measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess 'Overall Functioning and Well-being'. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being. Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered.
Time Frame	Baseline to End of Treatment

Outcome Measure Data

Analysis Population Description

Analysis limited to patients who completed baseline and at least one survey while on treatment up to end of treatment. Evaluation was based on actual regimen received versus regimen to which patient was randomized.

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV	PrOD With RBV	PrOD
Arm/Group Description:	Subjects will take EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg tablet): 1 to 3 tablets, once or twice daily (dosage and duration per discretion of provider)	Subjects will take EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) without Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider) RBV (Ribavirin) 200mg tablet: 1 to 3 tablets, once or twice daily at discretion of provider. Total daily dosage ranged from 200 to 1200 mg.	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider) SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration as HCV provider discretion)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets, once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dosage ranging from 200 - 1200 mg.	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). Treatment duration as per HCV provider ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)
Overall Number of Participants Analyzed	9	84	5	61	61	29
Median (Full Range); Unit of Measure: score on a scale
	0.0; (-21.9 to 16.4)	4.3; (-32.8 to 43.0)	4.7; (-9.4 to 7.8)	4.7; (-39.8 to 47.7)	3.1; (-50.0 to 71.9)	8.6; (-19.7 to 31.3)

19. Primary Outcome

Title	Mean Change in HCV-PRO (Functional Well-being) EBR/GZR vs. SOF/LDV Score-Phase 2
Description	HCV-PRO, a survey designed to assess functional status of patients with HCV and measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess functional well-being. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being. Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered. End of Treatment -Baseline were used to calculate CHANGE in outcome. Number of subjects reflects participants from both Phase 1 and 2.
Time Frame	End of Treatment - Baseline

Outcome Measure Data

Analysis Population Description

Patients with completed Baseline and End of Treatment HCV-PRO survey who started treatment by arm as treated (Period 2)

Arm/Group Title	EBR/GZR With RBV	EBR/GZR	SOF/LDV With RBV	SOF/LDV
Arm/Group Description:	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV (at discretion of provider) for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet orally once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dose ranging from 200 mg to 1200 mg.	Patients received EBR/GZR (elbasvir/grazoprevir) once daily without RBV (at discretion of provider) for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet orally once daily with or without food for 12 to 16 weeks (duration per provider discretion)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dosage ranged from 200 to 1200 mg.	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)
Overall Number of Participants Analyzed	40	413	10	226
Mean (Standard Deviation); Unit of Measure: score on a scale
	3.2 (18.6)	6.1 (15.7)	6.3 (10.7)	6.8 (18.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBR/GZR, SOF/LDV
	Comments	Analysis based on RBV free regimens in consideration that RBV usage was determined by provider and not study randomization. Population includes patients who started treatment by arm as treated.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -3.6 to 2.1
	Estimation Comments	CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.

20. Primary Outcome

Title	16 Wk EBR/GZR With RBV Efficacy on Patients With HCV RASs
Description	Efficacy of Hepatitis C Virus (HCV) Treatment with Zepatier (Elbasvir/Grazobevir) with Ribavirin (RBV) for 16 weeks when used in Genotype 1a patients with Baseline RASs (NS5a Resistance Associated Substitutions or RAPs -Resistance Associated Polymorphisms). Efficacy defined as HCV RNA undetectable 12 weeks post treatment. Table excludes Genotype 1b patients.
Time Frame	12 weeks post treatment

Outcome Measure Data

Analysis Population Description

All Genotype 1a patients who started treatment by arm randomized (Elbasvir/Grazobevir) with Baseline RAS at any location (28, 30, 31, or 93)

Arm/Group Title	EBR/GZR With RBV-16 Weeks
Arm/Group Description:	Subjects received EBR/GZR (elbasvir/grazoprevir) once daily with Ribavirin (RBV) for 16 weeks (as per provider discretion) EBR/GZR: Elbasvir/grazoprevir (50/100mg tablet) 1 tablet once daily with or without food RBV (200 mg tablet): 1-3 tablets once or twice daily for 16 weeks (dosage and duration at discretion of provider). Total dosage ranging from 200 mg to 1200 mg daily.
Overall Number of Participants Analyzed	38
Measure Type: Count of Participants; Unit of Measure: Participants
	34 89.5%

21. Secondary Outcome

Title	Treatment Non-Adherence Probability Estimates
Description	The Voils Medication Adherence Survey (VMAS) was used to evaluate medication adherence during HCV treatment. Participants responded to three questions about the extent of adherence during the past seven days of treatment (during early and late on-treatment occasions). Participants responded using a five-point ordinal scale of missed dosing from 1 (none of the time) to 5 (all of the time). On each occasion participants were coded as being "Non-adherent" if any response was > 1, otherwise they were coded as "Adherent". Probability estimates of percentage of patients reporting non-adherence were calculated per HCV treatment (Direct Acting Antiviral-DAA) regimen: 1)EBR/GZV (elbasvir/grazoprevir, 2)SOF/LDV (sofosbuvir/ledipasvir), 3)PrOD
Time Frame	12-16 weeks of HCV treatment

Outcome Measure Data

Analysis Population Description

Analysis is limited to participants to patients who started treatment prior to January 2017 (last day patient started on PrOD treatment)

Arm/Group Title	EBR/GZR	SOF/LDV	PrOD
Arm/Group Description:	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with or without RBV for 12 to 16 weeks (provider discretion) EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets, once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dosage ranging from 200-1200 mg.	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with or without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with or without Ribavirin ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks (treatment duration as per HCV provider) Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks RBV (200 mg tablet): 1-3 tablets once or twice daily for 12 to 24 weeks (dosage and duration at discretion of provider)
Overall Number of Participants Analyzed	151	108	146
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	23; (17 to 29)	19; (10 to 27)	26; (19 to 33)

22. Secondary Outcome

Title	Change in HCV-associated Symptoms (PROMIS Measures) After HCV Treatment Initiation
Description	Change in HCV-associated symptoms was calculated as the mean differences of mean scores from multiple surveys from the NIH Patient-Reported Outcomes Measurement Information System (PROMIS)-- Fatigue, nausea, belly pain, sleep disturbance, and diarrhea) and functional status (well-being) when comparing baseline to early post-treatment and late post treatment surveys. Mean change scores were calculated by comparing baseline to early post-treatment (1 yr) and late post-treatment (approximately 3 years) surveys. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement.Negative numbers suggest better symptoms (improvement in HCV-associated symptoms). PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.HCV-PRO positive estimates suggest baseline functional well-being improvement.
Time Frame	1 year post treatment discontinuation (Early post-tx)

Outcome Measure Data

Analysis Population Description

Analysis includes all patients who started treatment on either EBR/GZR or SOF/LDV regimen and is limited to patients who completed surveys. Analysis does not decipher between RBV usage given RBV usage was based on HCV provider selection and not study randomization

Arm/Group Title		EBR/GZR Regimen	SOF/LDV Regimen
Arm/Group Description:		Patients received elbasvir/grazoprevir tablet tablet once daily with or without RBV (at discretion of provider) for 12 to 16 weeks (provider discretion) elbasvir/grazoprevir: Elbasvir/grazoprevir (50/100mg) tablet once daily with food and with RBV: Ribavirin (200 mg/pill) 1-3 pills/day, 1-2 times/day. Total daily dosage ranged from 200 to 1200 mg.	Patients received 1 tablet SOF/LDV(sofosbuvir/ledipasvir) orally once daily with or without ribavirin (RBV) (per discretion of provider) with or without food 12 to 24 weeks SOF/LDV/sofosbuvir/ledipasvir: Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks (treatment duration is per discretion of HCV provider) RBV: Ribavirin (200mg pill) 1-3 pills, once or twice/day -dosage at discretion of provider. Total daily dosage ranged from 200 to 1200 mg.
Overall Number of Participants Analyzed		507	286
Mean (95% Confidence Interval); Unit of Measure: units on a scale
Nausea	Number Analyzed	505 participants	285 participants
		0.00; (-2.34 to 2.35)	-4.99; (-8.16 to -1.81)
Belly Pain	Number Analyzed	503 participants	283 participants
		-0.82; (-3.52 to 1.87)	-6.47; (-10.09 to -2.84)
Diarrhea	Number Analyzed	504 participants	282 participants
		-1.12; (-3.46 to 1.22)	-5.77; (-8.91 to -2.64)
Fatigue	Number Analyzed	506 participants	285 participants
		-2.08; (-4.74 to 0.58)	-7.59; (-11.17 to -4.01)
Sleep Disturbance	Number Analyzed	505 participants	283 participants
		0.65; (-0.70 to 2.00)	-1.72; (-3.81 to 0.37)
Cognitive Impairment	Number Analyzed	507 participants	282 participants
		-0.54; (-2.43 to 1.35)	-4.48; (-7.12 to -1.83)
HCV-PRO	Number Analyzed	507 participants	286 participants
		8.02; (3.94 to 12.11)	9.90; (4.27 to 15.52)

23. Secondary Outcome

Title	Post-treatment Progression/Regression of Liver Disease-Fib-4
Description	Mean change (delta) in FIB-4, an indirect non-invasive measure of liver fibrosis, calculated as baseline median -long term follow up median, following SVR after any of the study treatment regimens. Change in FIB-4 where negative values indicate improvement in liver fibrosis score and positive values indicate worsening of fibrosis score. There is no upper or lower limit for change. FIB-4 = age (years) * AST(IU/L)/Platelets (10^3/L) * ALT^.5(IU/L). In general, Score of 0-1.29 is low risk for advanced fibrosis, 1.30-1.67: intermediate risk for advanced liver fibrosis, >2.67: high risk for advanced fibrosis.
Time Frame	Baseline to up to 3 years post treatment discontinuation

Outcome Measure Data

Analysis Population Description

Population analyzed limited to cirrhotic patients who had two separate FIB-4 values collected as part of standard care and achieved SVR (defined as undetectable HCV 24 weeks post treatment). Given pragmatic trial design, availability of fibrosis markers is limited thereby restricting analysis (substantially limited sample size) to difference in fibrosis markers following SVR with any HCV treatment used in study.

Arm/Group Title	EBR/GZR, SOF/LDV or PrOD Based HCV Treatment
Arm/Group Description:	Elbasvir/grazoprevir (EBR/GZR): (50/100mg) tablet once daily with food for 12 to 16 weeks with or without RBV (Ribavirin usage as per provider discretion). Sofosbuvir/ledipasvir (SOF/LDV)/ (400/90 mg) 1 tablet once daily for approximately 12 to 24 weeks (treatment duration is per discretion of HCV provider) with or without RBV (RBV usage as per provider discretion): PrOD: Two ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily for 12 to 24 weeks + RBV (provider discretion) ombitasvir/paritaprevir/ritonavir (Phase 1 only): (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider) Dasabuvir: 250 mg daily for 12 to 24 weeks RBV: Ribavirin 200 to 600 mg once or twice daily RBV (Ribavirin)- 200mg pill, 1-3 pills/day once or twice daily (use and dosing per discretion of HCV provider).
Overall Number of Participants Analyzed	108
Median (Full Range); Unit of Measure: score on a scale
	-1.36; (-11.02 to 10.67)

24. Secondary Outcome

Title	Change in Functional Status (HCV-PRO) Within Treatment
Description	HCV-PRO score, a validated PROMIS survey used to evaluate overall functioning and well-being in HCV patients, was utilized to compare long-term 'within treatment' changes of functional well-being. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive estimate (Post treatment to baseline) suggests baseline functional well-being improvement. Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered.
Time Frame	Treatment start date up to 2 years post-treatment

Outcome Measure Data

Analysis Population Description

Analysis limited to patients who completed HCV-PRO assessments during post-treatment. For this safety analysis, regimen is based on treatment received versus treatment to which patient was randomized. Arms with and without RBV are combined in consideration that usage of RBV was decided by HCV provider and not part of study randomization.

Arm/Group Title	EBR/GZR Regimen	SOF/LDV Regimen
Arm/Group Description:	Subjects will take EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with or without Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg to 600mg tablet): 1 to 3 tablets once or twice daily (dosage and duration per discretion of provider)	Subjects will take 1 tablet SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with or without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)
Overall Number of Participants Analyzed	498	295
Mean (95% Confidence Interval); Unit of Measure: score on a scale
9 months post treatment	8.02; (3.94 to 12.11)	9.90; (4.27 to 15.52)
20 months post treatment	9.87; (5.48 to 14.27)	11.54; (5.07 to 18.02)

25. Secondary Outcome

Title	Number of Participants With Adverse Events That Caused Treatment Discontinuation-EBR/GZR vs. LDV/SOF
Description	The number of participants with adverse events that led to early treatment discontinuation (defined as duration less than originally prescribed treatment regimen)
Time Frame	Treatment start date through treatment completion (up to 24 weeks)

Outcome Measure Data

Analysis Population Description

As randomized and treated population during Phase 1 and 2 (See Period 1). Analysis based on HCV DAA regimen randomization per study. Differentiation between RBV usage was not included in analysis given that RBV was not part of study randomization but rather decided by HCV provider.

Arm/Group Title	EBR/GZR Regimen	SOF/LDV Regimen
Arm/Group Description:	Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with or without Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg to 600mg pill): 1 to 3 pill once or twice daily (dosage and duration per discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with or without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg pill: 1 to 3 pills once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dosage ranged from 200 to 1200 mg.
Overall Number of Participants Analyzed	700	428
Measure Type: Count of Participants; Unit of Measure: Participants
	12 1.7%	4 0.9%

26. Secondary Outcome

Title	HCV SVR Durability -No Cirrhosis
Description	Number/Percentage of patients with persistence of viral cure, SVR (SVR = Sustained Virologic Response)- defined as undetectable HCV RNA at least 24 weeks following HCV Treatment.
Time Frame	24 weeks post-end of treatment up to 153 weeks

Outcome Measure Data

Analysis Population Description

Analysis limited to patients who have HCV RNA result at least 24 weeks after end of treatment regimen as per period 1 (As randomized).

Arm/Group Title	EBR/GZR	EBR/GZR With Ribavirin	SOF/LDV	SOF/LDV With RBV	PrOD	PrOD With RBV
Arm/Group Description:	Patients received EBR/GZV tablet (elbasvir/grazoprevir) once daily for 12 to 16 weeks EBR/GZV (50/100mg) tablet: 1 tablet once daily with or without food 12 to 16 weeks	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily (with or without food) for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets, once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dosage ranged from 200 to 1200 mg.	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks (treatment duration as per HCV provider) Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV) ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily with food for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider) Dasabuvir (250 mg tablet): 1 tablet once or twice daily with food for 12 to 24 weeks (dosage at discretion of provider) RBV (200 mg tablet): 1-3 tablets once or twice daily for 12 to 24 weeks (dosage and duration at discretion of provider)
Overall Number of Participants Analyzed	255	17	146	2	14	36
Measure Type: Count of Participants; Unit of Measure: Participants
	255 100.0%	17 100.0%	146 100.0%	2 100.0%	14 100.0%	36 100.0%

27. Secondary Outcome

Title	HCV SVR Durability-Patients With Cirrhosis
Description	Percentage of Cirrhotic patients with persistence of viral cure, SVR, (SVR= Sustained Virologic Response) defined as undetectable HCV RNA at least 24 weeks following HCV Treatment.
Time Frame	Up to 132 weeks post HCV treatment

Outcome Measure Data

Analysis Population Description

Analysis limited to patients who had HCV viral load result at least 24 weeks after treatment and analyzed as per randomized (Period 1)

Arm/Group Title	EBR/GZR	EBR/GZR With RBV	SOF/LDV	SOF/LDV With RBV	PrOD	PrOD With RBV
Arm/Group Description:	Patients received EBR/GZR tablet (elbasvir/grazoprevir) once daily for 12 to 16 weeks EBR/GZR (50/100mg) tablet: 1 tablet once daily with or without food 12 to 16 weeks	Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV (Ribavirin) for 12 to 16 weeks EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily (with or without food) for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks (treatment duration as per HCV provider) Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks	PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV) ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily with food for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider) Dasabuvir (250 mg tablet): 1 tablet once or twice daily with food for 12 to 24 weeks (dosage at discretion of provider) RBV (200 mg tablet): 1-3 tablets once or twice daily for 12 to 24 weeks (dosage and duration at discretion of provider)
Overall Number of Participants Analyzed	43	7	35	7	6	7
Measure Type: Count of Participants; Unit of Measure: Participants
	43 100.0%	7 100.0%	35 100.0%	7 100.0%	6 100.0%	7 100.0%

28. Secondary Outcome

Title	Impact of Baseline NS5A RASs on Treatment Outcomes-Phase 2
Description	Number of participants who achieved SVR (sustained virologic response), defined as undetectable HCV RNA 12 weeks post-treatment with RASs (Resistant Associated Substitutions) after treatment with EBR/GZR or SOF/LDV regimen
Time Frame	12 weeks post HCV treatment

Outcome Measure Data

Analysis Population Description

Analysis is based on as assigned by randomization and patients with available RAS data. Exploratory RAS analysis is grouped by DAA regimen with or without RBV given 1)RBV usage was decided by HCV provider and not part of study randomization and small sample size (limited number of RAS in regimens with RBV)

Arm/Group Title		EBR/GZR Regimen	SOF/LDV Regimen
Arm/Group Description:		Patients received EBR/GZR (elbasvir/grazoprevir) once daily for 12 to 16 weeks (duration of treatment per provider discretion) with or without Ribavirin (RBV) (per provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks RBV(Ribavirin) (200mg to 600mg tablet): 1 to 3 tablets once or twice daily (usage, dosage and duration per discretion of provider) (Total dosage ranging from 200 mg to 1200 mg daily)	Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with or without ribavirin (RBV) (per discretion of provider) SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)
Overall Number of Participants Analyzed		560	337
Measure Type: Count of Participants; Unit of Measure: Participants
With NS5a RAS	Number Analyzed	54 participants	47 participants
		47 87.0%	42 89.4%
Without NS5a RAS	Number Analyzed	506 participants	290 participants
		485 95.8%	286 98.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBR/GZR Regimen, SOF/LDV Regimen
	Comments	[Not Specified]
	Type of Statistical Test	Equivalence
	Comments	Pre-specified equivalence range +/-5%
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -15.3 to 11.3
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	28 weeks. Adverse events collected up until final viral outcome is determined (approximately 12 weeks after HCV treatment completion).
Adverse Event Reporting Description	An adverse event (AE) is any untoward medical occurrence abstracted from the submitted patient medical records. In order to evaluate the safety profiles of the evaluated regimens, all safety analyses were performed based on 'actual treatment received' (as described in Period 2) rather than treatment to which subject was 'randomized'
Arm/Group Title	EBR/GZR		EBR/GZR With RBV		SOF/LDV With RBV		SOF/LDV		PrOD With RBV		PrOD
Arm/Group Description	Patients received EBR/GZR (elbasvir/grazoprevir) tablet once daily without RBV for 12 to 16 weeks (provider discretion) EBR/GZR: Elbasvir/grazoprevir (50/100mg tablet) 1 tablet once daily with or without food		Patients received EBR/GZR (elbasvir/grazoprevir tablet) tablet once daily with Ribavirin (RBV) for 12 to 16 weeks (provider discretion) EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food with RBV (200 to 600 mg once or twice daily) for 12 to 16 weeks		Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider) SOF/LDV (Sofosbuvir/Ledipasvir) (400/90 mg tablet) 1 tablet taken daily for approximately 12 to 24 weeks with RBV (Ribavirin) 200 mg: 1-3 pills, one to two times daily (dosage at discretion of HCV provider). Total daily dosage ranged fro 200 to 1200 mg.		Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks (treatment duration per discretion of provider) SOF/LDV (Sofosbuvir/Ledipasvir )(400/90 mg tablet) 1 tablet orally taken daily for approximately 12 to 24 weeks		PrOD (ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV) (treatment at duration provider discretion) ombitasvir/paritaprevir/ritonavir: 2 tablets orally once daily (12.5/75/50mg) for 12 to 24 weeks Dasabuvir (250 mg tablet): 1 tablet orally once or twice daily for 12 to 24 weeks Ribavirin (200 mg pill): 200 to 600 mg once or twice daily (dosage at provider discretion). Total daily dosage ranged from 200 to 1200 mg.		Patients received PrOD orally (ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV) (provider discretion) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg): 2 tablets taken once orally daily for 12 to 24 weeks (treatment duration as per HCV provider) Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks
All-Cause Mortality
	EBR/GZR		EBR/GZR With RBV		SOF/LDV With RBV		SOF/LDV		PrOD With RBV		PrOD
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	6/664 (0.90%)		0/56 (0.00%)		0/15 (0.00%)		4/394 (1.02%)		1/99 (1.01%)		0/47 (0.00%)
Serious Adverse Events
	EBR/GZR		EBR/GZR With RBV		SOF/LDV With RBV		SOF/LDV		PrOD With RBV		PrOD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/664 (4.52%)		2/56 (3.57%)		0/15 (0.00%)		6/394 (1.52%)		5/99 (5.05%)		0/47 (0.00%)
Cardiac disorders
Chest Pain † 1	0/664 (0.00%)	0	0/56 (0.00%)	0	0/15 (0.00%)	0	1/394 (0.25%)	1	1/99 (1.01%)	1	0/47 (0.00%)	0
Gastrointestinal disorders
Abdominal Pain † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Femoral hernia, obstructive † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Gastric ulcer perforation † 1 [1]	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Gastrointestinal haemorrhage † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Small intestinal obstruction † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
General disorders
Drug Withdrawal Syndrome † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Immune system disorders
Hypersensitivity † 1	0/664 (0.00%)	0	0/56 (0.00%)	0	0/15 (0.00%)	0	1/394 (0.25%)	1	0/99 (0.00%)	0	0/47 (0.00%)	0
Infections and infestations
Cellulitis † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Gastroenteritis viral † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Hepatitis B † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Osteomyelitis † 1	0/664 (0.00%)	0	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	1/99 (1.01%)	1	0/47 (0.00%)	0
Pneumonia † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	3/394 (0.76%)	3	0/99 (0.00%)	0	0/47 (0.00%)	0
Injury, poisoning and procedural complications
Fall † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Gun shot wound † 1	0/664 (0.00%)	0	0/56 (0.00%)	0	0/15 (0.00%)	0	1/394 (0.25%)	1	0/99 (0.00%)	0	0/47 (0.00%)	0
Hip fracture † 1	0/664 (0.00%)	0	0/56 (0.00%)	0	0/15 (0.00%)	0	1/394 (0.25%)	1	0/99 (0.00%)	0	0/47 (0.00%)	0
Overdose † 1	2/664 (0.30%)	2	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	1/99 (1.01%)	1	0/47 (0.00%)	0
Road traffic accident † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Thermal burn † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Toxicity to various agents † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Metabolism and nutrition disorders
Gout † 1	0/664 (0.00%)	0	0/56 (0.00%)	0	0/15 (0.00%)	0	1/394 (0.25%)	1	0/99 (0.00%)	0	0/47 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back Pain † 1	0/664 (0.00%)	0	0/56 (0.00%)	0	0/15 (0.00%)	0	1/394 (0.25%)	1	0/99 (0.00%)	0	0/47 (0.00%)	0
Pain in Extremity † 1	0/664 (0.00%)	0	0/56 (0.00%)	0	0/15 (0.00%)	0	1/394 (0.25%)	1	0/99 (0.00%)	0	0/47 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroendocrine carcinoma † 1	0/664 (0.00%)	0	1/56 (1.79%)	1	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Papillary thyroid cancer † 1	0/664 (0.00%)	0	1/56 (1.79%)	1	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Nervous system disorders
Adjustment Disorder † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Cerebrovascular Accident † 2	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	1/394 (0.25%)	1	0/99 (0.00%)	0	0/47 (0.00%)	0
Haemorrhagic stroke † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Neuropathy peripheral † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Spinal Hematoma † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Syncope † 1	0/664 (0.00%)	0	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	1/99 (1.01%)	1	0/47 (0.00%)	0
Psychiatric disorders
Alcohol withdrawal Syndrome † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Completed Suicide † 1	0/664 (0.00%)	0	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	1/99 (1.01%)	1	0/47 (0.00%)	0
Drug Abuse † 1	0/664 (0.00%)	0	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	1/99 (1.01%)	1	0/47 (0.00%)	0
Mania † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Mental status change † 2	2/664 (0.30%)	2	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Self-injurious ideation † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Renal and urinary disorders
Renal failure acute † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease † 2	2/664 (0.30%)	2	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Dyspnoea † 1	2/664 (0.30%)	2	0/56 (0.00%)	0	0/15 (0.00%)	0	1/394 (0.25%)	1	0/99 (0.00%)	0	0/47 (0.00%)	0
Respiratory failure † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Surgical and medical procedures
Drug Detoxification † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Vascular disorders
Arteriovenous fistula † 1	1/664 (0.15%)	1	0/56 (0.00%)	0	0/15 (0.00%)	0	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Deep Vein Thrombosis † 1	0/664 (0.00%)	0	0/56 (0.00%)	0	0/15 (0.00%)	0	1/394 (0.25%)	1	0/99 (0.00%)	0	0/47 (0.00%)	0
Peripheral ischaemia † 1	0/664 (0.00%)	0	0/56 (0.00%)	0	0/15 (0.00%)	0	1/394 (0.25%)	1	0/99 (0.00%)	0	0/47 (0.00%)	0
1 Term from vocabulary, MedDRA (15.1); 2 Term from vocabulary, MedDra; † Indicates events were collected by systematic assessment; [1] Gastric ulcer perforation
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	EBR/GZR		EBR/GZR With RBV		SOF/LDV With RBV		SOF/LDV		PrOD With RBV		PrOD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	298/664 (44.88%)		46/56 (82.14%)		8/15 (53.33%)		184/394 (46.70%)		74/99 (74.75%)		32/47 (68.09%)
Blood and lymphatic system disorders
Anaemia † 1 [1]	2/664 (0.30%)	2	17/56 (30.36%)	17	2/15 (13.33%)	2	0/394 (0.00%)	0	20/99 (20.20%)	20	0/47 (0.00%)	0
Cardiac disorders
Chest Pain † 1	10/664 (1.51%)	10	1/56 (1.79%)	1	1/15 (6.67%)	1	9/394 (2.28%)	9	3/99 (3.03%)	3	0/47 (0.00%)	0
Gastrointestinal disorders
Abdominal discomfort † 1	7/664 (1.05%)	7	1/56 (1.79%)	1	1/15 (6.67%)	1	2/394 (0.51%)	2	3/99 (3.03%)	3	0/47 (0.00%)	0
Nausea † 1	54/664 (8.13%)	54	12/56 (21.43%)	12	3/15 (20.00%)	3	34/394 (8.63%)	34	23/99 (23.23%)	23	5/47 (10.64%)	5
Diarrhoea † 1	45/664 (6.78%)	45	3/56 (5.36%)	3	2/15 (13.33%)	2	19/394 (4.82%)	19	5/99 (5.05%)	5	3/47 (6.38%)	3
Abdominal Pain † 1	11/664 (1.66%)	11	5/56 (8.93%)	5	1/15 (6.67%)	1	11/394 (2.79%)	11	3/99 (3.03%)	3	0/47 (0.00%)	0
Constipation † 1	16/664 (2.41%)	16	5/56 (8.93%)	5	0/15 (0.00%)	0	12/394 (3.05%)	12	2/99 (2.02%)	2	2/47 (4.26%)	2
Dyspepsia † 1	5/664 (0.75%)	5	4/56 (7.14%)	4	1/15 (6.67%)	1	3/394 (0.76%)	3	0/99 (0.00%)	0	2/47 (4.26%)	2
Vomiting † 1	13/664 (1.96%)	13	3/56 (5.36%)	3	0/15 (0.00%)	0	13/394 (3.30%)	13	8/99 (8.08%)	8	1/47 (2.13%)	1
Abdominal Pain Upper † 1	8/664 (1.20%)	8	2/56 (3.57%)	2	1/15 (6.67%)	1	9/394 (2.28%)	9	1/99 (1.01%)	1	1/47 (2.13%)	1
Decreased Appetite † 1	9/664 (1.36%)	9	2/56 (3.57%)	2	1/15 (6.67%)	1	5/394 (1.27%)	5	3/99 (3.03%)	3	2/47 (4.26%)	2
Hepatobiliary disorders
Hyperbilirubinaemia † 1	0/664 (0.00%)	0	3/56 (5.36%)	3	0/15 (0.00%)	0	0/394 (0.00%)	0	1/99 (1.01%)	1	0/47 (0.00%)	0
Cholelithiasis † 1	0/664 (0.00%)	0	0/56 (0.00%)	0	1/15 (6.67%)	1	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Infections and infestations
Influenza like illness † 1	18/664 (2.71%)	18	3/56 (5.36%)	3	0/15 (0.00%)	0	7/394 (1.78%)	7	2/99 (2.02%)	2	0/47 (0.00%)	0
Injury, poisoning and procedural complications
Fall † 1	3/664 (0.45%)	3	0/56 (0.00%)	0	1/15 (6.67%)	1	3/394 (0.76%)	3	0/99 (0.00%)	0	0/47 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back Pain † 1	15/664 (2.26%)	15	3/56 (5.36%)	3	0/15 (0.00%)	0	12/394 (3.05%)	12	0/99 (0.00%)	0	0/47 (0.00%)	0
Arthralgia † 1	17/664 (2.56%)	17	1/56 (1.79%)	1	1/15 (6.67%)	1	13/394 (3.30%)	13	4/99 (4.04%)	4	0/47 (0.00%)	0
Musculoskeletal Pain † 1	2/664 (0.30%)	2	1/56 (1.79%)	1	1/15 (6.67%)	1	3/394 (0.76%)	3	0/99 (0.00%)	0	0/47 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate Cancer † 1	0/664 (0.00%)	0	0/56 (0.00%)	0	1/15 (6.67%)	1	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Nervous system disorders
Dizziness † 1	15/664 (2.26%)	15	7/56 (12.50%)	7	0/15 (0.00%)	0	11/394 (2.79%)	11	3/99 (3.03%)	3	1/47 (2.13%)	1
Fatigue † 1	105/664 (15.81%)	105	18/56 (32.14%)	18	5/15 (33.33%)	5	82/394 (20.81%)	82	35/99 (35.35%)	35	5/47 (10.64%)	5
Headache † 1	94/664 (14.16%)	94	12/56 (21.43%)	12	1/15 (6.67%)	1	68/394 (17.26%)	68	15/99 (15.15%)	15	9/47 (19.15%)	9
Insomnia † 1	26/664 (3.92%)	26	6/56 (10.71%)	6	1/15 (6.67%)	1	10/394 (2.54%)	10	8/99 (8.08%)	8	3/47 (6.38%)	3
Tremor † 1	0/664 (0.00%)	0	0/56 (0.00%)	0	1/15 (6.67%)	1	0/394 (0.00%)	0	0/99 (0.00%)	0	0/47 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1 [2]	9/664 (1.36%)	9	8/56 (14.29%)	8	0/15 (0.00%)	0	11/394 (2.79%)	11	9/99 (9.09%)	9	1/47 (2.13%)	1
Bronchitis † 1	5/664 (0.75%)	5	3/56 (5.36%)	3	0/15 (0.00%)	0	2/394 (0.51%)	2	2/99 (2.02%)	2	0/47 (0.00%)	0
Cough † 1	15/664 (2.26%)	15	3/56 (5.36%)	3	0/15 (0.00%)	0	14/394 (3.55%)	14	3/99 (3.03%)	3	0/47 (0.00%)	0
Nasal Congestion † 1	2/664 (0.30%)	2	0/56 (0.00%)	0	1/15 (6.67%)	1	3/394 (0.76%)	3	0/99 (0.00%)	0	0/47 (0.00%)	0
Skin and subcutaneous tissue disorders
Pruritus † 1	10/664 (1.51%)	10	3/56 (5.36%)	3	0/15 (0.00%)	0	2/394 (0.51%)	2	4/99 (4.04%)	4	4/47 (8.51%)	4
Rash † 1	10/664 (1.51%)	10	2/56 (3.57%)	2	1/15 (6.67%)	1	5/394 (1.27%)	5	3/99 (3.03%)	3	3/47 (6.38%)	3
Vascular disorders
Oedema Peripheral † 1 [3]	12/664 (1.81%)	12	1/56 (1.79%)	1	1/15 (6.67%)	1	4/394 (1.02%)	4	1/99 (1.01%)	1	0/47 (0.00%)	0
1 Term from vocabulary, MedDRA (15.1); † Indicates events were collected by systematic assessment; [1] Anemia; [2] Dyspnea; [3] Peripheral edema Edema Peripheral

Limitations and Caveats

This pragmatic trial allowed patients who were randomized to SOF/LDV but unable to obtain SOF/LDV (due to limitations in access from insurance, etc.) to be treated with the accessible, alternative DAA regimens. This contributed to the variance from 'as randomized' population to the 'as treated' population. Rapidly changing HCV landscape led to discontinuation of PrOD treatment regimen and modification of initial analysis plan including reduction of original sample size.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Lauren Morelli
• Organization: UF Hepatology Research at CTRB
• Phone: 352-273-9508
• EMail: lauren.morelli@medicine.ufl.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Evon DM, Dong M, Reeve BB, Peter J, Michael L, Lok AS, Nelson DR, Stewart PW. Sustainable and equivalent improvements in symptoms and functional well-being following viral cure from ledipasvir/sofosbuvir versus elbasvir/grazoprevir for chronic hepatitis C infection: Findings from the randomized PRIORITIZE trial. J Viral Hepat. 2022 Sep;29(9):795-806. doi: 10.1111/jvh.13716. Epub 2022 Jun 15.

Sulkowski MS, Moon JS, Sherman KE, Morelli G, Darling JM, Muir AJ, Khalili M, Fishbein DA, Hinestrosa F, Shiffman ML, Di Bisceglie A, Rajender Reddy K, Pearlman B, Lok AS, Fried MW, Stewart PW, Peter J, Wadsworth S, Kixmiller S, Sloan A, Vainorius M, Horne PM, Michael L, Dong M, Evon DM, Segal JB, Nelson DR; PRIORITIZE Study Team. A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study. Hepatology. 2021 Dec;74(6):2952-2964. doi: 10.1002/hep.32053. Epub 2021 Aug 26.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT02786537
• Other Study ID Numbers: 16-1234; PCORI-1503-27891 ( Other Identifier: PCORI ); IRB201501162 ( Other Identifier: New UF IRB-01 )
• First Submitted: May 17, 2016
• First Posted: June 1, 2016
• Results First Submitted: May 26, 2020
• Results First Posted: November 24, 2020
• Last Update Posted: December 6, 2021