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

NCT04694612 | Unknown Phase 3 DMC

• 1 other identifier: 683-2020
• Study Type: interventional
• Target: 676
• Locations: 1 country
• Sites: 2

Brief 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clearance \& quicker symptomatic relief however, most of these studies lack strong statistical significance \& are not peer-reviewed.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.

Conditions

Covid19

Outcome Measures

Primary Outcomes (2)

• clinical improvements in mild cases

  Mild cases: Time to clinical improvements is defined as recovery in two out of the three common symptoms that includes fever (body temperature more than 99.5 degrees F), cough, and headache/malaise (scored more than 3 in a pain likert scale of 1 to 10). Moderate cases: Time to clinical improvement defined as Improvement in at least 2 out 3 selected common symptoms as above as in mild cases PLUS improvement in shortness of breath (\*For the assessment of clinical improvement in moderate cases, we did not include imaging findings because radiological changes lag behind clinical improvement by a few weeks.)

  5 day

• clinical improvements in moderate cases

  Moderate Case: Efficacy of Favipiravir on clinical improvement among COVID-19 patients with moderate symptoms compared to Remdesivir

  10 days

Secondary Outcomes (6)

• Clinical deterioration in mild & moderate cases

  up to 14 days

• Radiological improvement in moderate cases

  11 days

• 28 days mortality in mold & moderate cases

  28 days

• symptomatic improvement or worsening in mild & moderate cases

  28 days

• compare change in SARS-CoV-2 viral load in nasopharyngeal swab in mild & moderate cases

  6 days

Study Arms (2)

Mild condition

PLACEBO COMPARATOR

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. Duration of treatment : 5 days in each group

Drug: Favipiravir; Drug: Placebo

Moderate condition

ACTIVE COMPARATOR

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 Inj Remdesivir 200 mg IV on day 1, followed by 100 mg IV daily. Duration of treatment : 10 days in Favipiravir group \& 5 days in Remdesivir group

Drug: Favipiravir; Drug: Remdesivir

Interventions

Favipiravir DRUG

Comparison of clinical improvement and clinical deterioration between those receiving Favipiravir compared to placebo in the patients with mild COVID-19

Also known as: Favir 200

Mild condition; Moderate condition

Placebo DRUG

Comparison of clinical improvement and clinical deterioration between those receiving Favipiravir compared to placebo in the patients with mild COVID-19

Mild condition

Remdesivir DRUG

Comparison of clinical improvement and clinical deterioration between those receiving Favipiravir compared to Remdesivir Injection in the patients with moderate COVID-19

Moderate condition

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Minimum 18 - 80 years of age
• 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)
• Signed informed consent provided by patient's or patient's healthcare proxy.
• Fulfills enrollment criteria ( within 6 days of symptoms onset)
• Willing to practice celibacy OR take contraception during the study \& within 7 days after treatment
• Mild clinical condition with at least 3 of these of these symptoms : fever, cough, malaise/headache
• Moderate clinical condition with at least 3 of these of these symptoms : fever, cough, malaise/headache

You may not qualify if:

• Pregnant (female of childbearing age with positive urine pregnancy test) or miscarriage or within 2 weeks after delivery
• 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
• Creatinine clearance (Cockcroft-Gault Equation) \< 30 ml/min or having hemodialysis/peritoneal dialysis
• Known allergy or hypersensitivity to Favipiravir
• Gout or history of gout or hyperuricemia two times the upper limit of normal
• If using Remdesivir, Lopinavir-ritonavir, Hydroxychloroquine or any other antiviral drug with potential effect against SARS-CoV-2 virus
• Lactating female
• Asymptomatic COVID-19 cases
• (\*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)

Sponsors & Collaborators

• Nepal Health Research Council: lead

Study Sites (2)

Armed Police Force Hospital

Kathmandu, Bagmati, 44600, Nepal

RECRUITING

Charak Memorial Hospital

Pokhara, Gandaki, 33800, Nepal

RECRUITING

MeSH Terms

Conditions

COVID-19

Interventions

favipiravir; remdesivir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Prabhat Adhikari, MD

CONTACT

+977-9843003527; prabhatadhikari@gmail.com

Janak Koirala, MD

CONTACT

+977 9818762117; jkoirala2002@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: 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 comorbidity (presence or absence of self-reported diabetes, hypertension, Coronary Artery Disease, Coronary Heart Failure, Cancer or auto-immune disease). The permuted block (30 patients per block) randomization sequence, including stratification, will be prepared by a statistician using STATA-15 software. Once an eligible patient is enrolled in the participating center, the physician will call the central hotline that will inform the physician about the allocation based on the sequence. Eligible patients allocated to the respective arm will receive individually numbered packs, according to the sequence order as informed by the hotline.

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: January 5, 2021
• Study Start: January 1, 2021
• Primary Completion: March 31, 2021
• Study Completion: May 31, 2021
• Last Updated: January 5, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

NE (2)