Efficacy of favipiravir in adults with mild COVID-19: a randomized, double-blind, multicentre, placebo-controlled clinical trial

Abstract

Objective To evaluate whether favipiravir reduces the time to viral clearance as documented by negative SARS-CoV-2 RT-PCR in mild COVID-19 cases compared to placebo. Methods In this randomized, double-blinded, multicenter, and placebo-controlled trial, adults with PCR confirmed mild COVID-19 were recruited in an outpatient setting at seven medical facilities across Saudi Arabia. Participants were randomized in a 1:1 ratio to receive either favipiravir 1800 mg by mouth twice daily on day one followed by 800 mg twice daily (n=112) or a matching placebo (n=119), for a total of 5 to 7 days. The primary outcome was the effect of favipiravir on reducing the time to viral clearance (by PCR test) within 15 days of starting the treatment compared to the placebo group. The trial included the following secondary outcomes: symptom resolution, hospitalization, ICU admissions, adverse events, and 28-day mortality. Results 231 patients were randomized and began the study (median age, 37 [interquartile range: 32-44] years; 155 [67%] men), and 112 (48.5%) were assigned to the treatment group and 119 (51.5%) into the placebo group. The data and safety monitoring board (DSMB) recommended stopping enrollment because of futility at the interim analysis. The median time to viral clearance was 10 (IQR: 6-12) days in the favipiravir group and 8 (IQR: 6-12) days in the placebo group, with a hazard ratio of 0.87 for the favipiravir group (95% CI 0.571 to 1.326; p-value =0.51). The median time to clinical recovery was 7 days (IQR: 4-11) in the favipiravir group and 7 days (IQR: 5-10) in the placebo group. There was no difference between the two groups on the secondary outcome of hospital admission. There were no drug-related severe adverse events. Conclusion In this clinical trial, favipiravir therapy in mild COVID-19 patients did not reduce the time to viral clearance within 15 days of starting the treatment. Clinical Trial Registration ClinicalTrials.gov identifier ( NCT04464408 ): https://clinicaltrials.gov/ct2/show/NCT04464408 .

Real-World Experience with Favipiravir for the Treatment of Mild-to-Moderate COVID-19 in India

“…This was also reported in a multicentric double-blind randomised controlled trial, where the median time to clinical recovery was seven days. 14 Similarly, in a phase III placebo-controlled RCT of Moderate COVID-19 patients who did not require oxygen, patients who received Favipiravir had a three-day shorter clinical cure, with a significant difference (p = 0.0136) and a hazard ratio of 1.59 (1.02–2.48). 15 In another metaanalysis 16 of 11 eligible studies, 5 of which included a comparison group, the Favipiravir group had significantly greater clinical improvement on days 7 and 14.…”

Health Economic Burden of COVID-19 in Saudi Arabia

“…Additionally, a number of medications were initially thought to be beneficial against COVID-19, such as favipiravir and hydroxychloroquine. However, studies have proven that these medications have no effect against COVID-19 25 . These developments represent additional reasons for the high cost of treating COVID-19 patients.…”

Immune-related therapeutics: an update on antiviral drugs and vaccines to tackle the COVID-19 pandemic

“…However, in a clinical trial conducted in Saudi Arabia, in which 231 COVID-19 patients (treatment group) were treated with favipiravir and a placebo group of 119 patients were kept in a similar environment, the median time for viral clearance was 10 days in the treatment group versus 8 days in the placebo group, and the median time for clinical recovery was 7 days in both groups. This trial suggests that favipiravir does not shorten the time required for viral clearance [ 32 ]. The available clinical trials indicate that favipiravir relieves cough and fever but fails to accelerate viral clearance [ 33 ].…”