Clinical trial NCT04542694: Study of Favipiravir Compared to Standard of Care in Hospitalized Patients With COVID-19
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Keywords: Favipiravir
Areplivir
COVID-19
SARS-CoV-2
2019-nCoV
Lead sponsor: Promomed, LLC
Sponsor class: OTHER
First posted: 2020-09-09
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Rate of Clinical Status Improvement
timeFrame: By Visit 3, approximately 10 days
measure: Time to Clinical Improvement
timeFrame: 28 days
Secondary outcomes:
measure: Rate of Viral Elimination by Day 10
timeFrame: 10 days
measure: Time Before the End of Fever
timeFrame: 28 days
measure: Change in the Level of Lung Damage According to CT
timeFrame: Days 15, 21, 28
measure: Rate of Transfer to the Intensive Care Unit
timeFrame: 28 Days
measure: Rate of the Use of Non-invasive Lung Ventilation
timeFrame: 28 Days
measure: Rate of the Use of Mechanical Ventilation
timeFrame: 28 Days
measure: Mortality
timeFrame: 28 Days
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: State Clinical Hospital №50
city: Ryazan'
country: Russian Federation
facility: Regional Clinic Hospital of Ryazan
city: Saint Petersburg
country: Russian Federation
facility: City Hospital N40 of Kurortny District
city: Saransk
country: Russian Federation
facility: Medical institute Ogarev Mordovia State university
city: Smolensk
country: Russian Federation
facility: Smolensk clinical hospital №1
Study officials:
affiliation: Moscow State Clinical Hospital №50
name: Dmitriy Pushkar
role: PRINCIPAL_INVESTIGATOR
References: