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 Description

Brief Summary:

Phase 1 of this study compared the effectiveness of 3 approved DAA (direct-acting antiviral) HCV treatment regimens to learn whether they worked equally well under real-world conditions. Phase 2 of this study began early 2017 with removal of 1 DAA regimen, limiting randomization to just 2 FDA approved DAA regimens. Patients receiving HCV therapy in community and academic clinics were offered the opportunity to consent to be randomly assigned to one of three (phase 1) or one of two (phase 2) regimens and observed for outcomes. Once randomized, all medical care, laboratory testing, and any disease or side effect management were assumed by usual care conditions, and patient-reported outcomes were collected outside clinic in keeping with pragmatic design principles.

Condition or disease	Intervention/treatment	Phase
Chronic Hepatitis C	Drug: SOF/LDV (sofosbuvir/ledipasvir); Drug: PrOD (ombitasvir/paritaprevir/ritonavir with dasabuvir) (Phase 1 only); Drug: EBR/GZR (elbasvir/grazoprevir); Drug: Ribavirin	Phase 4

Detailed Description:

In Phase 1 of this study, consented patients were randomized to 1 of the following 3 HCV DAA treatments: 1) Harvoni® (SOF/LDV) 2) Viekira Pak™ (PrOD) 3) Zepatier™ (EBR/GZR) with the optional addition of Ribavirin (RBV) and the length of treatment determined by the individual provider.

In Phase 2 of this study, consented patients were randomized to 1 of 2 FDA approved HCV treatments: Harvoni® or Zepatier™. Both Phase 1 and Phase 2 subjects had up to 1 tablespoon of blood drawn for HCV resistance testing and future biorepository testing (following appropriate additional consent). The results of testing determined whether a genotype 1a subject randomized to Zepatier would be provided 12 or 16 wks of Zepatier.

Following enrollment/randomization, participants completed patient reported outcome questionnaires (PROs) via electronic device or telephone. Following baseline/randomization, participants were asked to complete surveys again at Wk 4 of treatment, End of Treatment, 1 and 3 year post treatment. Patients continued standard medical care throughout study. Data was abstracted from test results and medical records throughout treatment and for up to 3 years post treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1275 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: THE PRIORITIZE STUDY: A Pragmatic, Randomized Study of Oral Regimens for Hepatitis C: Transforming Decision-Making for Patients, Providers, and Stakeholders
• Study Start Date: June 2016
• Actual Primary Completion Date: June 13, 2019
• Actual Study Completion Date: September 2, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: EBR/GZR (elbasvir/grazoprevir) with RBV; Patients received 1 EBR/GZR (elbasvir/grazoprevir) (Zepatier) tablet (50/100mg) once daily for 12 to 16 weeks (provider discretion) with Ribavirin (RBV) 200 mg/tablet, 1-3/day, taken 1-2 times per day (dosage at discretion of provider).	Drug: EBR/GZR (elbasvir/grazoprevir); Elbasvir/grazoprevir (50/100mg) tablet once daily with or without food with or without RBV for 12 to 16 weeks; Other Name: Zepatier; Drug: Ribavirin; 200 mg pills (1-3 pills, 1-2 times per day); Other Name: RBV
Active Comparator: EBR/GZR (elbasvir/grazoprevir); Patients received 1 EBR/GZR (elbasvir/grazoprevir) tablet (50/100 mg) once daily for 12 to 16 weeks (provider discretion) (without Ribavirin)	Drug: EBR/GZR (elbasvir/grazoprevir); Elbasvir/grazoprevir (50/100mg) tablet once daily with or without food with or without RBV for 12 to 16 weeks; Other Name: Zepatier
Active Comparator: SOF/LDV (sofosbuvir/ledipasvir) with RBV; 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) (at discretion of provider). RBV taken as 200 mg/tablet(capsule), 1-3 pills/day, 1-2 times/day.	Drug: SOF/LDV (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); Other Name: Harvoni® (sofosbuvir/ledipasvir); Drug: Ribavirin; 200 mg pills (1-3 pills, 1-2 times per day); Other Name: RBV
Active Comparator: SOF/LDV (sofosbuvir/ledipasvir); 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)	Drug: SOF/LDV (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); Other Name: Harvoni® (sofosbuvir/ledipasvir)
Active Comparator: PrOD (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir) with RBV (Phase 1 only); 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.	Drug: 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); Other Name: Viekira Pak/Viekira
Active Comparator: PrOD (ombitasvir/paritaprevir/ritonavir and dasabuvir); 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)	Drug: 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); Other Name: Viekira Pak/Viekira; Drug: Ribavirin; 200 mg pills (1-3 pills, 1-2 times per day); Other Name: RBV

Outcome Measures

Primary Outcome Measures :

1. Sustained Virologic Response (SVR12) mITT With Imputation-Phase 1 and 2 EBR/GZR, SOF/LDV [ Time Frame: 12 weeks post-treatment ]

   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.

2. Phase 1/2 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation) [ Time Frame: 12-24 weeks post HCV treatment ]

   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.

3. Phase 1-Sustained Virologic Response (SVR12) mITT With Imputation [ Time Frame: 12 weeks post-treatment ]

   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.

4. Phase 1 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation) [ Time Frame: 12 -24 weeks post-treatment ]

   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.

5. Mean Change in Headache-PRO Scores -Phase 1 [ Time Frame: Baseline to On-Treatment ]
   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.
6. Mean Change in Headache-EBR/GZR and SOF/LDV [ Time Frame: Baseline to On-Treatment ]
   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
7. Median Change in Headache -Phase 1 [ Time Frame: 12 weeks (Baseline and Average On-treatment Score) ]
   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
8. Median Change in Headache-Phase 2 [ Time Frame: Baseline -on Treatment (12-16 weeks) ]
   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
9. Mean Change in Nausea/Vomiting PRO Score -Phase 1 [ Time Frame: Baseline to On-Treatment ]

   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.

10. Mean Change in Nausea/Vomiting PROMIS Score -EBR/GZR vs. LDV/SOF [ Time Frame: Baseline and Average On-Treatment Score ]

    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.

11. Median Change in Nausea PRO Score -Phase 1 [ Time Frame: Baseline to end of treatment ]

    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.

12. Median Change in Nausea PROMIS Score-EBR/GZR SOF/LDV [ Time Frame: Baseline- On Treatment (up to 16 weeks) ]

    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.

13. Mean Change in Fatigue PRO Score -Phase 1 [ Time Frame: Baseline to On-treatment ]
    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.
14. Mean Change in Fatigue PRO -EBR/GZR vs SOF/LDV [ Time Frame: Baseline and Average On-Treatment Score ]
    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.
15. Median Change in Fatigue -Phase 1 [ Time Frame: Baseline to End of Treatment ]
    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.
16. Median Change in Fatigue-Phase 2 [ Time Frame: Baseline-On Treatment (up to 16 weeks) ]
    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.
17. Mean Change in HCV- PRO- Phase 1 [ Time Frame: Baseline to End of Treatment ]

    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.

18. Median Change in HCV-PRO (Overall Well Being) -Phase 1 [ Time Frame: Baseline to End of Treatment ]

    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.

19. Mean Change in HCV-PRO (Functional Well-being) EBR/GZR vs. SOF/LDV Score-Phase 2 [ Time Frame: End of Treatment - Baseline ]

    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.

20. 16 Wk EBR/GZR With RBV Efficacy on Patients With HCV RASs [ Time Frame: 12 weeks post treatment ]

    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.

Secondary Outcome Measures :

1. Treatment Non-Adherence Probability Estimates [ Time Frame: 12-16 weeks of HCV treatment ]
   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
2. Change in HCV-associated Symptoms (PROMIS Measures) After HCV Treatment Initiation [ Time Frame: 1 year post treatment discontinuation (Early post-tx) ]
   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.
3. Post-treatment Progression/Regression of Liver Disease-Fib-4 [ Time Frame: Baseline to up to 3 years post treatment discontinuation ]
   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.
4. Change in Functional Status (HCV-PRO) Within Treatment [ Time Frame: Treatment start date up to 2 years post-treatment ]

   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.

5. Number of Participants With Adverse Events That Caused Treatment Discontinuation-EBR/GZR vs. LDV/SOF [ Time Frame: Treatment start date through treatment completion (up to 24 weeks) ]
   The number of participants with adverse events that led to early treatment discontinuation (defined as duration less than originally prescribed treatment regimen)
6. HCV SVR Durability -No Cirrhosis [ Time Frame: 24 weeks post-end of treatment up to 153 weeks ]
   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.
7. HCV SVR Durability-Patients With Cirrhosis [ Time Frame: Up to 132 weeks post HCV treatment ]
   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.
8. Impact of Baseline NS5A RASs on Treatment Outcomes-Phase 2 [ Time Frame: 12 weeks post HCV treatment ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• HCV Genotype 1a or 1b
• Adult patients (age 18 years or older)
• Patients being prescribed HCV treatment who can begin treatment with any of the three HCV treatments being studied (Harvoni (SOF/LDV), Viekira Pak (PrOD) (Phase 1 only), or Zepatier (EBR/GZR))

Exclusion Criteria:

• Inability to provide written informed consent
• HARVONI® is not a covered drug on benefits formulary
• Current or historical evidence of hepatic decompensation (variceal bleeding, hepatic encephalopathy, or ascites)
• Child Pugh (CTP) B or C Cirrhosis (documented CTP calculation is required)
• Pregnant or breastfeeding women

Contacts and Locations

Locations

United States, Arkansas

Liver Wellness Center

Little Rock, Arkansas, United States, 72205

United States, California

Stanford University

Palo Alto, California, United States, 94304

UCSD Medical Center

San Diego, California, United States, 92103

UCSF/Zuckerberg San Francisco General Hospital and Trauma Center

San Francisco, California, United States, 94110

Univ of California, San Francisco

San Francisco, California, United States, 94143

United States, Connecticut

Yale University Digestive Diseases

New Haven, Connecticut, United States, 06520

United States, District of Columbia

Georgetown University

Washington, District of Columbia, United States, 20007

Howard University

Washington, District of Columbia, United States, 20060

United States, Florida

University of Florida

Gainesville, Florida, United States, 32610-0272

University of Florida, Jacksonville

Jacksonville, Florida, United States, 32209

University of Miami/Schiff Center for Liver Diseases

Miami, Florida, United States, 33136

Orlando Immunology Center

Orlando, Florida, United States, 32803

United States, Georgia

Internal Medicine Associates of Wellstar Atlanta Medical Center

Atlanta, Georgia, United States, 30312

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

Northwestern University

Chicago, Illinois, United States, 60647

United States, Indiana

Indiana University Medical Center

Indianapolis, Indiana, United States, 46202

United States, Maryland

John Hopkins University

Lutherville, Maryland, United States, 21093

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

United States, Minnesota

University of Minnesota

Minneapolis, Minnesota, United States, 55455

United States, Mississippi

GI Associates & Endoscopy Center

Flowood, Mississippi, United States, 39232

United States, Missouri

Saint Louis University

Saint Louis, Missouri, United States, 63104

United States, Nebraska

University of Nebraska Medical Ctr

Omaha, Nebraska, United States, 68198

United States, New Mexico

Southwest CARE Center

Santa Fe, New Mexico, United States, 87505

United States, New York

Mt. Sinai Beth Israel

New York, New York, United States, 10003

New York Langone Medical Center

New York, New York, United States, 10016

Weill Cornell Medical College

New York, New York, United States, 10021

Columbia University Medical Center

New York, New York, United States, 10032

Mountain View Medical Center

Valatie, New York, United States, 12184

United States, North Carolina

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States, 27599

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, Ohio

University of Cincinnati

Cincinnati, Ohio, United States, 45267

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, Texas

Research Specialist of Texas

Houston, Texas, United States, 77030

United States, Virginia

Bon Secours St. Mary 's Hospital of Richmond (Liver Institute of Virginia)

Richmond, Virginia, United States, 23226

Virginia Commonwealth University

Richmond, Virginia, United States, 23284

United States, Washington

Virginia Mason Medical Center

Seattle, Washington, United States, 98101

University of Washington

Seattle, Washington, United States, 98104

Sponsors and Collaborators

University of Florida

Patient-Centered Outcomes Research Institute

Merck Sharp & Dohme LLC

AbbVie

Investigators

• Principal Investigator: David R Nelson, MD; University of Florida

  Study Documents (Full-Text)

Documents provided by University of Florida:

Study Protocol and Statistical Analysis Plan  [PDF] September 18, 2018

More Information

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 Posted: June 1, 2016
• Results First Posted: November 24, 2020
• Last Update Posted: December 6, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by University of Florida:

Hepatitis C

Additional relevant MeSH terms:

Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Blood-Borne Infections; Communicable Diseases; Flaviviridae Infections; Hepatitis, Chronic; Ritonavir; Ribavirin; Sofosbuvir; Grazoprevir; Ledipasvir; Elbasvir-grazoprevir drug combination; HIV Protease Inhibitors; Viral Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents