Efficacy of Favipiravir in Treatment of Mild & Moderate COVID-19 Infection in Nepal

• Status: Recruiting
• Trial end date: 2021-05-31
• Target enrollment: 0
• Participant gender: All

Summary

COVID-19 has affected almost all countries in the world. Every other country is constantly working towards its treatment and development of vaccines, with little to no success so far. Recently, several regimens have been tried as antiviral medicine. Among these medicines, Favipiravir is considered a broad-spectrum antiviral with the spectrum of activity noted against a wide range of RNA viruses & a good oral antiviral drug with > 97% bioavailability. It has already proved its safety profile as it has received FDA indication for drug-resistant Influenza. There has been increasing evidence of favorable outcome against COVID-19 in terms of early viral clearance & quicker symptomatic relief however, most of these studies lack strong statistical significance & are not peer-reviewed. Subjects will be categorized into two arms based on the severity of infection due to COVID-19 defined by NMC guidelines. Each arm will have respective two groups as the study drug group and control group. Based on the sample size calculation, subjects will be stratified & randomly enrolled in the study after checking the eligibility criteria at the screening visit. About 276 mild patients will be recruited for this trial and 400 moderate patients (including 10% loss ). Study arm groups will receive a Favipiravir treatment of 1800 mg PO BID on day 1, then 800 mg PO BID from day 2 onwards and control groups will receive the same quantity of Placebo. Treatment will be continued till 5 days after for mild groups and 10 days for moderate groups. Eligible patients will be randomly assigned (1:1) to either Favipiravir or Placebo among mild cases; and Favipiravir or Remdesivir among moderate cases. Randomization will be stratified by age group (18 to 40 years, 40 to 60 years and 60 to 80 years) and co-morbidity. The permuted block (30 patients per block) randomization sequence, including stratification, will be prepared by a statistician using STATA-15 software. Eligible patients will be allocated to the respective arm and will receive individually numbered packs, according to the sequence order as informed by the hotline. Informed written consent will be taken from the participants before commencing the study. All safety data, patient's baseline, clinical outcome data, data from endpoints and variables should be reported by the clinician and his/her team in a pre-instructed case report form (CRF) via a designated website.

It is our assumption that if the study results come favorable, Favipiravir, when used in mild or moderate cases, might prevent progression of the disease to higher severity, helps achieve viral clearance early so as to positively impact disease transmission in the community, increase the quality of life by quicker symptom recovery & decrease health burden by shortening the length of stay at the hospital. These findings can also be useful in international scenarios where the world is looking for innovative measures to curb COVID-19 infection. The study findings will be disseminated within and outside the country and will be published in peer-reviewed journals.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nepal Health Research Council
• Treatments: Favipiravir; Remdesivir

Criteria

A. Inclusion Criteria:

1. Minimum 18 - 80 years of age

2. Clinical Diagnosis of COVID 19 with RT-PCR test for SARS-CoV-2 (If a patient is COVID19 positive based on Antigen test, they can participate in the trial while awaiting result form PCR test with Ct-value)

3. Signed informed consent provided by patient's or patient's healthcare proxy.

4. Fulfills enrollment criteria ( within 6 days of symptoms onset)

5. Willing to practice celibacy OR take contraception during the study & within 7 days after treatment

6. Mild clinical condition with at least 3 of these of these symptoms : fever, cough, malaise/headache

7. Moderate clinical condition with at least 3 of these of these symptoms : fever, cough, malaise/headache

B. Exclusion Criteria:

1. Pregnant (female of childbearing age with positive urine pregnancy test) or miscarriage or within 2 weeks after delivery

2. Severe or critical clinical condition as per NMC clinical guideline for COVID19 Chronic liver with ALT/AST increased 5 times higher than the upper limit of normal or with Child Pugh C

3. Creatinine clearance (Cockcroft-Gault Equation) < 30 ml/min or having hemodialysis/peritoneal dialysis

4. Known allergy or hypersensitivity to Favipiravir

5. Gout or history of gout or hyperuricemia two times the upper limit of normal

6. If using Remdesivir, Lopinavir-ritonavir, Hydroxychloroquine or any other antiviral drug with potential effect against SARS-CoV-2 virus

7. Lactating female

8. Asymptomatic COVID-19 cases

9. Mild COVID-19 cases not meeting the inclusion criteria symptoms

10. Moderate COVID-19 cases not meeting the inclusion criteria symptoms

(*All female patients age 18 - 50 years will be screened for pregnancy by urine test & any pregnant patient will be excluded. Also, the patient must be consented to take contraception or practice celibacy during the study period & until 7 days after treatment. Since the expected wash out period of the study drug Favipiravir is 10hrs minimum to 27.5hrs maximum (half life is 2-5.5hrs), it is a safe practice to avoid conception for 1 week after stopping the drug of interest)