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

COVID-19 Clinical Trial

Official title:

Open-label Randomized Multicenter Comparative Study on the Efficacy and Safety of Areplivir Film-coated Tablets (PROMOMED RUS LLC, Russia) in Patients Hospitalized With COVID-19

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04542694
• Other study ID #: FAV052020
• Status: Completed
• Phase: Phase 3
• Start date: May 21, 2020
• Est. completion date: August 20, 2020

Study information

• Verified date: November 2020
• Source: Promomed, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is open-labe randomized multicenter comparative Phase III study conducted in 5 medical facilities. The objective of the study is to assess the efficacy and safety of Favipiravir compared with the Standard of care (SOC) in hospitalized patients with moderate COVID-19 pneumonia.

Description:

Upon signing the informed consent form and screening, 200 eligible patients with polymerase chain reaction (PCR) confirmed COVID-19 are randomized at a 1:1 ratio to receive either Favipiravir 1600 mg twice a day (BID) on Day 1 followed by 600 mg BID on Days 2-14 (1600/600 mg), or SOC. The course of treatment by Favipiravir is 14 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: August 20, 2020
• Est. primary completion date: August 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Signing and dating of the Informed Consent Form of the Patient Information Leaflet (PIL) by patients.

2. Men and women aged 18 to 80 years inclusive at the time of signing the Informed Consent Form in PIL.

3. No difficulty with oral medication (e.g. swallowing disorder).

4. Patient diagnosed with "Coronavirus infection caused by SARS-CoV-2 (confirmed)1, moderate severity form*" established in accordance with the Interim Guidelines of the Russian Ministry of Health for the prevention, diagnosis and treatment of a new coronavirus infection (COVID-19), (revision 6 of 28.04.2020).

*Moderate severity form: fever above 38 °C, BR above 22/min, dyspnea during exercise, pneumonia (confirmed by lung CT), SpO2 < 95%, C reactive protein (CRP) serum level above 10 mg/l.

5. Patient should be hospitalized no more than 48 hours before the start of the study therapy.

6. Positive PCR result for presence of SARS-CoV-2 RNA at screening phase (results obtained within 7 days prior to screening are appropriate).

7. Patient's consent to use reliable contraceptive methods throughout the study and within 1 month for women and 3 months for men after its completion. Persons eligible for participation in the study: - Women who have a negative pregnancy test and use the following contraceptives: barrier method (condom or occlusive cap (diaphragm or cervical/vaulted cap)) or double barrier method of contraception (condom or occlusive cap (diaphragm or cervical/vaulted cap) plus spermicide (foam/gel/film/cream/suppository)). Women incapable of childbearing may also participate in the study (with past history of: hysterectomy, tubal ligation, infertility, menopause more than 1 year) or men with preserved reproductive function who use barrier contraceptives, as well as men with infertility or vasectomy in the past medical history.

Exclusion Criteria:

1. Hypersensitivity to favipiravir and/or other components of the study drug.

2. Impossibility of CT procedure (for example, gypsum dressing or metal structures in the field of imaging).

3. The need to use drugs from the list of prohibited therapy.

4. Need for treatment in the intensive care unit.

5. Impaired liver function (AST and/or ALT = 2 UNL and/or total bilirubin = 1.5 UNL) at the time of screening.

6. Impaired kidney function (creatinine clearance according to Cockcroft-Gault formula less than 45 ml/min) at the time of screening.

7. Positive testing for HIV, syphilis, hepatitis B and/or C.

8. Chronic heart failure FC III-IV according to New York Heart Association (NYHA) functional classification.

9. Malabsorption syndrome or other clinically significant gastrointestinal disease that may affect absorption of the study drug (non-correctable vomiting, diarrhea, ulcerative colitis, and others).

10. Malignancies in the past medical history.

11. Alcohol, pharmacological and/or drug addiction in the past medical history and/or at the time of screening.

12. Schizophrenia, schizoaffective disorder, bipolar disorder, or other history of mental pathology or suspicion of their presence at the time of screening.

13. Severe, decompensated or unstable somatic diseases (any disease or condition that threaten the patient's life or impair the patient's prognosis, and also make it impossible for him/her to participate in the clinical study).

14. Any history data that the investigating physician believes could lead to complication in the interpretation of the study results or create an additional risk to the patient as a result of his/her participation in the study.

15. Patient's unwillingness or inability to comply with procedures of the Study Protocol (in the opinion of physician investigator).

16. Pregnant or nursing women or women planning pregnancy.

17. Participation in another clinical study for 3 months prior to inclusion in the study.

18. Other conditions that, according to the physician investigator, prevent the patient from being included in the study.

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Favipiravir
200 mg coated tablets
• 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.

Locations

Country	Name	City	State
Russian Federation	State Clinical Hospital ?50	Moscow
Russian Federation	Regional Clinic Hospital of Ryazan	Ryazan'
Russian Federation	City Hospital N40 of Kurortny District	Saint Petersburg
Russian Federation	Medical institute Ogarev Mordovia State university	Saransk
Russian Federation	Smolensk clinical hospital ?1	Smolensk

Sponsors (1)

Lead Sponsor	Collaborator
Promomed, LLC

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Clinical Status Improvement	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	By Visit 3, approximately 10 days
Primary	Time to Clinical Improvement	Time (in days) to improvement in clinical status by WHO categorical ordinal scale of clinical status improvement.	28 days
Secondary	Rate of Viral Elimination by Day 10	Percentage of patients with elimination (clearance) of COVID-19 according to PCR data by day 10 (negative PCR results).	10 days
Secondary	Time Before the End of Fever	Time (in days) before the end of fever (body temperature < 37.2 ° C for 3 consecutive days without antipyretic medication).	28 days
Secondary	Change in the Level of Lung Damage According to CT	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)	Days 15, 21, 28
Secondary	Rate of Transfer to the Intensive Care Unit	Percentage of patients transferred to intensive care unit (% of patients).	28 Days
Secondary	Rate of the Use of Non-invasive Lung Ventilation	Percentage of cases with non-invasive lung ventilation (% of patients).	28 Days
Secondary	Rate of the Use of Mechanical Ventilation	Percentage of cases with mechanical lung ventilation (% of patients)	28 Days
Secondary	Mortality	Incidence of fatal cases (% of patients)	28 Days