Study of Favipiravir Compared to Standard of Care in Hospitalized Patients With COVID-19

• ClinicalTrials.gov Identifier: NCT04542694
• Recruitment Status: Completed
• First Posted: September 9, 2020
• Results First Posted: November 5, 2020
• Last Update Posted: November 5, 2020
• Sponsor: Promomed, LLC
• Information provided by (Responsible Party): Promomed, LLC

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: COVID-19
• Interventions: Drug: Favipiravir; Drug: Standard of care
• Enrollment: 200

Participant Flow

Recruitment Details
Pre-assignment Details	The study will randomize 200 patients. Given the possible non-inclusion of patients at the screening stage, the maximum number of patients to sign the Informed Consent Form in the Patient Information Leaflet and to participate in screening can be no more than 210 people.

Arm/Group Title	Favipiravir (Areplivir)	Standard of Care
Arm/Group Description	Arm 1 (n=100) receives the study drug Areplivir film-coated tablets: on day 1 of therapy - 1600 mg (8 tablets) 2 times a day; on days 2-14 of treatment - 600 mg (3 tablets) 2 times a day. The drug is taken orally every 12 hours, swallowing whole tablet without chewing and washing down with a glass of water. The course of treatment is 14 days. The test drug is administered in hospital setting under supervision of a clinical investigator. The test drug is not handed over to the patient. Favipiravir: 200 mg coated tablets	Arm 2 (n=100) patients receive standard therapy prescribed in accordance with the recommended treatment regimens included in the Interim Guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) approved by the Russian Ministry of Health (but not Favipiravir) by decision of the investigator and taking into account the availability of drugs at the study site. Might include hydroxychloroquine (with or without azithromycin), chloroquine, lopinavir/ritonavir or other recommended schemes. Standard therapy is administered in hospital setting. Discharge of patients from a hospital is carried out in accordance with the local practice of the study site in compliance with the current sanitary and epidemiological regime.
Period Title: Overall Study
Started	100	100
Completed	96	100
Not Completed	4	0
Reason Not Completed
The need for prohibited therapy	2	0
Adverse Event	1	0
Protocol Violation	1	0

Baseline Characteristics

Arm/Group Title		Favipiravir (Areplivir)	Standard of Care	Total
Arm/Group Description		Arm 1 (n=100) receives the study drug Areplivir film-coated tablets: on day 1 of therapy - 1600 mg (8 tablets) 2 times a day; on days 2-14 of treatment - 600 mg (3 tablets) 2 times a day. The drug is taken orally every 12 hours, swallowing whole tablet without chewing and washing down with a glass of water. The course of treatment is 14 days. The test drug is administered in hospital setting under supervision of a clinical investigator. The test drug is not handed over to the patient. Favipiravir: 200 mg coated tablets	Arm 2 (n=100) patients receive standard therapy prescribed in accordance with the recommended treatment regimens included in the Interim Guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) approved by the Russian Ministry of Health (but not Favipiravir) by decision of the investigator and taking into account the availability of drugs at the study site. Might include hydroxychloroquine (with or without azithromycin), chloroquine, lopinavir/ritonavir or other recommended schemes. Standard therapy is administered in hospital setting. Discharge of patients from a hospital is carried out in accordance with the local practice of the study site in compliance with the current sanitary and epidemiological regime. Standard of care: Drug: Standard of Care Standard of Care will be prescribed in accordance with the recommended treatment regimens presented in the Russian guidelines for the prevention, diagnosis and treatment of COVID-19 according to the decision of the Investigator. Other Name: Hydroxychloroquine, chloroquine, lopinavir/ritonavir, etc.	Total of all reporting groups
Overall Number of Baseline Participants		100	100	200
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	100 participants	100 participants	200 participants
		49.38 (13.18)	49.98 (13.06)	49.68 (13.09)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	100 participants	100 participants	200 participants
	Female	49 49.0%	54 54.0%	103 51.5%
	Male	51 51.0%	46 46.0%	97 48.5%
Race and Ethnicity Not Collected [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	0 participants	0 participants	0 participants
				0
		[1] Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Russia	Number Analyzed	100 participants	100 participants	200 participants
		100	100	200

Outcome Measures

1. Primary Outcome

Title	Rate of Clinical Status Improvement
Description	Rate of clinical status improvement by categorical ordinal scale of clinical status improvement by 2 or more categories by Day 10 WHO Ordinal Scale for Clinical Improvement (WHO-OSCI), 0 - uninfected (There are no clinical and virological signs of infection), 8 - dead, higher scores mean a worse outcome
Time Frame	By Visit 3, approximately 10 days

Outcome Measure Data

Analysis Population Description

Intent-tо-treat population

Arm/Group Title	Favipiravir (Areplivir)	Standard of Care
Arm/Group Description:	Arm 1 (n=100) receives the study drug Areplivir film-coated tablets: on day 1 of therapy - 1600 mg (8 tablets) 2 times a day; on days 2-14 of treatment - 600 mg (3 tablets) 2 times a day. The drug is taken orally every 12 hours, swallowing whole tablet without chewing and washing down with a glass of water. The course of treatment is 14 days. The test drug is administered in hospital setting under supervision of a clinical investigator. The test drug is not handed over to the patient. Favipiravir: 200 mg coated tablets	Arm 2 (n=100) patients receive standard therapy prescribed in accordance with the recommended treatment regimens included in the Interim Guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) approved by the Russian Ministry of Health (but not Favipiravir) by decision of the investigator and taking into account the availability of drugs at the study site. Might include hydroxychloroquine (with or without azithromycin), chloroquine, lopinavir/ritonavir or other recommended schemes. Standard therapy is administered in hospital setting. Discharge of patients from a hospital is carried out in accordance with the local practice of the study site in compliance with the current sanitary and epidemiological regime.
Overall Number of Participants Analyzed	100	100
Measure Type: Count of Participants; Unit of Measure: Participants
	27 27.0%	15 15.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favipiravir (Areplivir), Standard of Care
	Comments	A comparative analysis of the rate of clinical status improvement by 2 or more categories. The difference in percentages between the AREPLIVIR arm and the standard therapy arm (pa-pb)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0372
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	The difference in proportions
	Estimated Value	0.1313
	Confidence Interval	(2-Sided) 95%; -0.0004 to 0.2367
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Time to Clinical Improvement
Description	Time (in days) to improvement in clinical status by WHO categorical ordinal scale of clinical status improvement.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

patients who received at least one dose of the drug in the study and for whom there is data for at least one visit after the baseline

Arm/Group Title	Favipiravir (Areplivir)	Standard of Care
Arm/Group Description:	Arm 1 (n=100) receives the study drug Areplivir film-coated tablets: on day 1 of therapy - 1600 mg (8 tablets) 2 times a day; on days 2-14 of treatment - 600 mg (3 tablets) 2 times a day. The drug is taken orally every 12 hours, swallowing whole tablet without chewing and washing down with a glass of water. The course of treatment is 14 days. The test drug is administered in hospital setting under supervision of a clinical investigator. The test drug is not handed over to the patient. Favipiravir: 200 mg coated tablets	Arm 2 (n=100) patients receive standard therapy prescribed in accordance with the recommended treatment regimens included in the Interim Guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) approved by the Russian Ministry of Health (but not Favipiravir) by decision of the investigator and taking into account the availability of drugs at the study site. Might include hydroxychloroquine (with or without azithromycin), chloroquine, lopinavir/ritonavir or other recommended schemes. Standard therapy is administered in hospital setting. Discharge of patients from a hospital is carried out in accordance with the local practice of the study site in compliance with the current sanitary and epidemiological regime.
Overall Number of Participants Analyzed	100	100
Median (Inter-Quartile Range); Unit of Measure: days
	8; (6 to 10)	12; (7 to 12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favipiravir (Areplivir), Standard of Care
	Comments	Comparative analysis of time to clinical status improvement by categorical ordinal clinical improvement scale between the AREPLIVIR arm and the standard therapy arm
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	The difference in days
	Estimated Value	4
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Rate of Viral Elimination by Day 10
Description	Percentage of patients with elimination (clearance) of COVID-19 according to PCR data by day 10 (negative PCR results).
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

patients who received at least one dose of the drug in the study and for whom there is data for at least one visit after the baseline

Arm/Group Title	Favipiravir (Areplivir)	Standard of Care
Arm/Group Description:	Arm 1 (n=100) receives the study drug Areplivir film-coated tablets: on day 1 of therapy - 1600 mg (8 tablets) 2 times a day; on days 2-14 of treatment - 600 mg (3 tablets) 2 times a day. The drug is taken orally every 12 hours, swallowing whole tablet without chewing and washing down with a glass of water. The course of treatment is 14 days. The test drug is administered in hospital setting under supervision of a clinical investigator. The test drug is not handed over to the patient. Favipiravir: 200 mg coated tablets	Arm 2 (n=100) patients receive standard therapy prescribed in accordance with the recommended treatment regimens included in the Interim Guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) approved by the Russian Ministry of Health (but not Favipiravir) by decision of the investigator and taking into account the availability of drugs at the study site. Might include hydroxychloroquine (with or without azithromycin), chloroquine, lopinavir/ritonavir or other recommended schemes. Standard therapy is administered in hospital setting. Discharge of patients from a hospital is carried out in accordance with the local practice of the study site in compliance with the current sanitary and epidemiological regime.
Overall Number of Participants Analyzed	100	100
Measure Type: Count of Participants; Unit of Measure: Participants
	98 98.0%	79 79.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favipiravir (Areplivir), Standard of Care
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.00016
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	The difference in percentages
	Estimated Value	22.5
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Time Before the End of Fever
Description	Time (in days) before the end of fever (body temperature < 37.2 ° C for 3 consecutive days without antipyretic medication).
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

patients who received at least one dose of the drug in the study and for whom there is data for at least one visit after the baseline

Arm/Group Title	Favipiravir (Areplivir)	Standard of Care
Arm/Group Description:	Arm 1 (n=100) receives the study drug Areplivir film-coated tablets: on day 1 of therapy - 1600 mg (8 tablets) 2 times a day; on days 2-14 of treatment - 600 mg (3 tablets) 2 times a day. The drug is taken orally every 12 hours, swallowing whole tablet without chewing and washing down with a glass of water. The course of treatment is 14 days. The test drug is administered in hospital setting under supervision of a clinical investigator. The test drug is not handed over to the patient. Favipiravir: 200 mg coated tablets	Arm 2 (n=100) patients receive standard therapy prescribed in accordance with the recommended treatment regimens included in the Interim Guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) approved by the Russian Ministry of Health (but not Favipiravir) by decision of the investigator and taking into account the availability of drugs at the study site. Might include hydroxychloroquine (with or without azithromycin), chloroquine, lopinavir/ritonavir or other recommended schemes. Standard therapy is administered in hospital setting. Discharge of patients from a hospital is carried out in accordance with the local practice of the study site in compliance with the current sanitary and epidemiological regime.
Overall Number of Participants Analyzed	100	100
Median (Inter-Quartile Range); Unit of Measure: days
	4; (2 to 5)	5; (3 to 7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favipiravir (Areplivir), Standard of Care
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.052
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	1.55
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Change in the Level of Lung Damage According to CT
Description	Assessment of lung injury (degree of damage by "empirical" visual scale and % of patients) according to CT data comparing to baseline. The number of patients in whom by the end of therapy there was an improvement in the condition of the lungs (a decrease in the volume of the lesion according to CT)
Time Frame	Days 15, 21, 28

Outcome Measure Data

Analysis Population Description

The number of patients in whom by the end of therapy there was an improvement in the condition of the lungs (a decrease in the volume of the lesion according to CT)

Arm/Group Title	Favipiravir (Areplivir)	Standard of Care
Arm/Group Description:	Arm 1 (n=100) receives the study drug Areplivir film-coated tablets: on day 1 of therapy - 1600 mg (8 tablets) 2 times a day; on days 2-14 of treatment - 600 mg (3 tablets) 2 times a day. The drug is taken orally every 12 hours, swallowing whole tablet without chewing and washing down with a glass of water. The course of treatment is 14 days. The test drug is administered in hospital setting under supervision of a clinical investigator. The test drug is not handed over to the patient. Favipiravir: 200 mg coated tablets	Arm 2 (n=100) patients receive standard therapy prescribed in accordance with the recommended treatment regimens included in the Interim Guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) approved by the Russian Ministry of Health (but not Favipiravir) by decision of the investigator and taking into account the availability of drugs at the study site. Might include hydroxychloroquine (with or without azithromycin), chloroquine, lopinavir/ritonavir or other recommended schemes. Standard therapy is administered in hospital setting. Discharge of patients from a hospital is carried out in accordance with the local practice of the study site in compliance with the current sanitary and epidemiological regime.
Overall Number of Participants Analyzed	100	100
Measure Type: Count of Participants; Unit of Measure: Participants
	60 60.0%	40 40.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favipiravir (Areplivir), Standard of Care
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1953
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

6. Secondary Outcome

Title	Rate of Transfer to the Intensive Care Unit
Description	Percentage of patients transferred to intensive care unit (% of patients).
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

the number of patients who required transfer to the intensive care unit

Arm/Group Title	Favipiravir (Areplivir)	Standard of Care
Arm/Group Description:	Arm 1 (n=100) receives the study drug Areplivir film-coated tablets: on day 1 of therapy - 1600 mg (8 tablets) 2 times a day; on days 2-14 of treatment - 600 mg (3 tablets) 2 times a day. The drug is taken orally every 12 hours, swallowing whole tablet without chewing and washing down with a glass of water. The course of treatment is 14 days. The test drug is administered in hospital setting under supervision of a clinical investigator. The test drug is not handed over to the patient. Favipiravir: 200 mg coated tablets	Arm 2 (n=100) patients receive standard therapy prescribed in accordance with the recommended treatment regimens included in the Interim Guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) approved by the Russian Ministry of Health (but not Favipiravir) by decision of the investigator and taking into account the availability of drugs at the study site. Might include hydroxychloroquine (with or without azithromycin), chloroquine, lopinavir/ritonavir or other recommended schemes. Standard therapy is administered in hospital setting. Discharge of patients from a hospital is carried out in accordance with the local practice of the study site in compliance with the current sanitary and epidemiological regime.
Overall Number of Participants Analyzed	100	100
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Favipiravir (Areplivir), Standard of Care
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4975
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

7. Secondary Outcome

Title	Rate of the Use of Non-invasive Lung Ventilation
Description	Percentage of cases with non-invasive lung ventilation (% of patients).
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

the number of patients who required non-invasive lung ventilation

Arm/Group Title	Favipiravir (Areplivir)	Standard of Care
Arm/Group Description:	Arm 1 (n=100) receives the study drug Areplivir film-coated tablets: on day 1 of therapy - 1600 mg (8 tablets) 2 times a day; on days 2-14 of treatment - 600 mg (3 tablets) 2 times a day. The drug is taken orally every 12 hours, swallowing whole tablet without chewing and washing down with a glass of water. The course of treatment is 14 days. The test drug is administered in hospital setting under supervision of a clinical investigator. The test drug is not handed over to the patient. Favipiravir: 200 mg coated tablets	Arm 2 (n=100) patients receive standard therapy prescribed in accordance with the recommended treatment regimens included in the Interim Guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) approved by the Russian Ministry of Health (but not Favipiravir) by decision of the investigator and taking into account the availability of drugs at the study site. Might include hydroxychloroquine (with or without azithromycin), chloroquine, lopinavir/ritonavir or other recommended schemes. Standard therapy is administered in hospital setting. Discharge of patients from a hospital is carried out in accordance with the local practice of the study site in compliance with the current sanitary and epidemiological regime.
Overall Number of Participants Analyzed	100	100
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

8. Secondary Outcome

Title	Rate of the Use of Mechanical Ventilation
Description	Percentage of cases with mechanical lung ventilation (% of patients)
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

the number of patients who required mechanical lung ventilation

Arm/Group Title	Favipiravir (Areplivir)	Standard of Care
Arm/Group Description:	Arm 1 (n=100) receives the study drug Areplivir film-coated tablets: on day 1 of therapy - 1600 mg (8 tablets) 2 times a day; on days 2-14 of treatment - 600 mg (3 tablets) 2 times a day. The drug is taken orally every 12 hours, swallowing whole tablet without chewing and washing down with a glass of water. The course of treatment is 14 days. The test drug is administered in hospital setting under supervision of a clinical investigator. The test drug is not handed over to the patient. Favipiravir: 200 mg coated tablets	Arm 2 (n=100) patients receive standard therapy prescribed in accordance with the recommended treatment regimens included in the Interim Guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) approved by the Russian Ministry of Health (but not Favipiravir) by decision of the investigator and taking into account the availability of drugs at the study site. Might include hydroxychloroquine (with or without azithromycin), chloroquine, lopinavir/ritonavir or other recommended schemes. Standard therapy is administered in hospital setting. Discharge of patients from a hospital is carried out in accordance with the local practice of the study site in compliance with the current sanitary and epidemiological regime.
Overall Number of Participants Analyzed	100	100
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

9. Secondary Outcome

Title	Mortality
Description	Incidence of fatal cases (% of patients)
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

the number of patients who died

Arm/Group Title	Favipiravir (Areplivir)	Standard of Care
Arm/Group Description:	Arm 1 (n=100) receives the study drug Areplivir film-coated tablets: on day 1 of therapy - 1600 mg (8 tablets) 2 times a day; on days 2-14 of treatment - 600 mg (3 tablets) 2 times a day. The drug is taken orally every 12 hours, swallowing whole tablet without chewing and washing down with a glass of water. The course of treatment is 14 days. The test drug is administered in hospital setting under supervision of a clinical investigator. The test drug is not handed over to the patient. Favipiravir: 200 mg coated tablets	Arm 2 (n=100) patients receive standard therapy prescribed in accordance with the recommended treatment regimens included in the Interim Guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) approved by the Russian Ministry of Health (but not Favipiravir) by decision of the investigator and taking into account the availability of drugs at the study site. Might include hydroxychloroquine (with or without azithromycin), chloroquine, lopinavir/ritonavir or other recommended schemes. Standard therapy is administered in hospital setting. Discharge of patients from a hospital is carried out in accordance with the local practice of the study site in compliance with the current sanitary and epidemiological regime.
Overall Number of Participants Analyzed	100	100
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

10. Post-Hoc Outcome

Title	Amount of Patients Without Any Clinical Signs of Disease by the Completion of Therapy (Category 0 According to a WHO Categorical Ordinal Scale)
Description	[Not Specified]
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Favipiravir (Areplivir)	Standard of Care
Arm/Group Description:	Arm 1 (n=100) receives the study drug Areplivir film-coated tablets: on day 1 of therapy - 1600 mg (8 tablets) 2 times a day; on days 2-14 of treatment - 600 mg (3 tablets) 2 times a day. The drug is taken orally every 12 hours, swallowing whole tablet without chewing and washing down with a glass of water. The course of treatment is 14 days. The test drug is administered in hospital setting under supervision of a clinical investigator. The test drug is not handed over to the patient. Favipiravir: 200 mg coated tablets	Arm 2 (n=100) patients receive standard therapy prescribed in accordance with the recommended treatment regimens included in the Interim Guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) approved by the Russian Ministry of Health (but not Favipiravir) by decision of the investigator and taking into account the availability of drugs at the study site. Might include hydroxychloroquine (with or without azithromycin), chloroquine, lopinavir/ritonavir or other recommended schemes. Standard therapy is administered in hospital setting. Discharge of patients from a hospital is carried out in accordance with the local practice of the study site in compliance with the current sanitary and epidemiological regime.
Overall Number of Participants Analyzed	100	100
Measure Type: Count of Participants; Unit of Measure: Participants
	44 44.0%	10 10.0%

11. Post-Hoc Outcome

Title	The Number of Patients Achieved a Category Lower Than or Equal to 2 on the WHO Clinical Improvement Scale (They Were Discharged From Hospital)
Description	[Not Specified]
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Favipiravir (Areplivir)	Standard of Care
Arm/Group Description:	Arm 1 (n=100) receives the study drug Areplivir film-coated tablets: on day 1 of therapy - 1600 mg (8 tablets) 2 times a day; on days 2-14 of treatment - 600 mg (3 tablets) 2 times a day. The drug is taken orally every 12 hours, swallowing whole tablet without chewing and washing down with a glass of water. The course of treatment is 14 days. The test drug is administered in hospital setting under supervision of a clinical investigator. The test drug is not handed over to the patient. Favipiravir: 200 mg coated tablets	Arm 2 (n=100) patients receive standard therapy prescribed in accordance with the recommended treatment regimens included in the Interim Guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) approved by the Russian Ministry of Health (but not Favipiravir) by decision of the investigator and taking into account the availability of drugs at the study site. Might include hydroxychloroquine (with or without azithromycin), chloroquine, lopinavir/ritonavir or other recommended schemes. Standard therapy is administered in hospital setting. Discharge of patients from a hospital is carried out in accordance with the local practice of the study site in compliance with the current sanitary and epidemiological regime.
Overall Number of Participants Analyzed	100	100
Measure Type: Count of Participants; Unit of Measure: Participants
	90 90.0%	67 67.0%

12. Post-Hoc Outcome

Title	A Number of Patients With Fever Reduction Below 37.2 ° C by the 3rd Day of Therapy
Description	[Not Specified]
Time Frame	3 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Favipiravir (Areplivir)	Standard of Care
Arm/Group Description:	Arm 1 (n=100) receives the study drug Areplivir film-coated tablets: on day 1 of therapy - 1600 mg (8 tablets) 2 times a day; on days 2-14 of treatment - 600 mg (3 tablets) 2 times a day. The drug is taken orally every 12 hours, swallowing whole tablet without chewing and washing down with a glass of water. The course of treatment is 14 days. The test drug is administered in hospital setting under supervision of a clinical investigator. The test drug is not handed over to the patient. Favipiravir: 200 mg coated tablets	Arm 2 (n=100) patients receive standard therapy prescribed in accordance with the recommended treatment regimens included in the Interim Guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) approved by the Russian Ministry of Health (but not Favipiravir) by decision of the investigator and taking into account the availability of drugs at the study site. Might include hydroxychloroquine (with or without azithromycin), chloroquine, lopinavir/ritonavir or other recommended schemes. Standard therapy is administered in hospital setting. Discharge of patients from a hospital is carried out in accordance with the local practice of the study site in compliance with the current sanitary and epidemiological regime.
Overall Number of Participants Analyzed	100	100
Measure Type: Count of Participants; Unit of Measure: Participants
	60 60.0%	37 37.0%

Adverse Events

Time Frame	Safety assessment was carried out: up to 30 days for each patient and during the entire period of the study as a whole. Safety population: patients who have received at least one dose of the study drug and for whom there is an assessment of condition and/or AE for at least one time point after administration.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Favipiravir (Areplivir)	Standard of Care
Arm/Group Description	Arm 1 (n=100) receives the study drug Areplivir film-coated tablets: on day 1 of therapy - 1600 mg (8 tablets) 2 times a day; on days 2-14 of treatment - 600 mg (3 tablets) 2 times a day. The drug is taken orally every 12 hours, swallowing whole tablet without chewing and washing down with a glass of water. The course of treatment is 14 days. The test drug is administered in hospital setting under supervision of a clinical investigator. The test drug is not handed over to the patient. Favipiravir: 200 mg coated tablets	Arm 2 (n=100) patients receive standard therapy prescribed in accordance with the recommended treatment regimens included in the Interim Guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) approved by the Russian Ministry of Health (but not Favipiravir) by decision of the investigator and taking into account the availability of drugs at the study site. Might include hydroxychloroquine (with or without azithromycin), chloroquine, lopinavir/ritonavir or other recommended schemes. Standard therapy is administered in hospital setting. Discharge of patients from a hospital is carried out in accordance with the local practice of the study site in compliance with the current sanitary and epidemiological regime.
All-Cause Mortality
	Favipiravir (Areplivir)	Standard of Care
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/100 (0.00%)	0/100 (0.00%)
Serious Adverse Events
	Favipiravir (Areplivir)	Standard of Care
	Affected / at Risk (%)	Affected / at Risk (%)
Total	3/100 (3.00%)	0/100 (0.00%)
Cardiac disorders
Aortic valve stenosis † 1 [1]	1/100 (1.00%)	0/100 (0.00%)
General disorders
Multiple organ failure syndrome † 1 [2]	1/100 (1.00%)	0/100 (0.00%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure † 1 [2]	1/100 (1.00%)	0/100 (0.00%)
1 Term from vocabulary, MedDRA; † Indicates events were collected by systematic assessment; [1] According to investigators, the causal relationship with the study drug was estimated as "doubtful", SAE was associated with the presence of concomitant diseases, i.e. type 2 diabetes mellitus, obesity, and hyperthyroidism.; [2] According to investigators, the causal relationship with the study drug was estimated as "unrelated", SAE was associated with the presence of concomitant diseases, i.e. type 2 diabetes mellitus, obesity, and hyperthyroidism.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Favipiravir (Areplivir)	Standard of Care
	Affected / at Risk (%)	Affected / at Risk (%)
Total	25/100 (25.00%)	28/100 (28.00%)
Hepatobiliary disorders
Increased alanine aminotransferase activity † 1 [1]	18/100 (18.00%)	19/100 (19.00%)
Increased aspartate aminotransferase activity † 1 [2]	13/100 (13.00%)	13/100 (13.00%)
1 Term from vocabulary, MedDRA; † Indicates events were collected by systematic assessment; [1] According to investigators, the causal relationship with the study drug was estimated as "unrelated" in 22.2%; [2] According to investigators, the causal relationship with the study drug / standard therapy was estimated as "unrelated" in 69.2% /61.5%

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Academician Dmitry Pushkar
• Organization: A.I. Yevdokimov Moscow State University of Medicine and Dentistry of the Ministry of Healthcare of the Russian Federation
• Phone: +7495-609-67-00
• EMail: dmitry.pushkar@gmail.com

• Responsible Party: Promomed, LLC
• ClinicalTrials.gov Identifier: NCT04542694
• Other Study ID Numbers: FAV052020
• First Submitted: September 4, 2020
• First Posted: September 9, 2020
• Results First Submitted: October 11, 2020
• Results First Posted: November 5, 2020
• Last Update Posted: November 5, 2020