Multi-centre, randomised, double-blinded trial of favipiravir versus placebo for treatment of mild Covid-19 in outpatients in South Africa

Since the outbreak of SARS-CoV-2 there have been more than 9-million confirmed Covid-19 cases and close to 500,000 deaths. Despite the significant loss of life, economic and social disruption that this disease has already caused throughout the world, the vulnerability of people and healthcare systems will persist until effective and safe interventions are discovered. Remdesivir and corticosteroids have shown benefit in hospitalised patients with severe Covid-19, but there are still no proven efficacious and safe interventions for ambulatory patients with mild disease. Identifying interventions that reduce duration of illness and Covid-19 hospitalisations is a public health priority. Favipiravir is a broad-spectrum oral antiviral with direct activity against RNA viruses, including SARS-CoV-2. It is approved for treatment-resistant influenza and has an excellent safety profile in over 40 clinical studies. In a non-randomised trial for Covid-19, favipiravir was associated with a faster decline in viral PCR titres, faster resolution on lung imaging, and significantly fewer adverse events in comparison to lopinarvir/ritonavir. Over 3,000 patients have been administered favipiravir under compassionate use in Japan with high recovery rates observed in both mild and moderate disease. We propose a pragmatic, multi-centre, randomised, double-blinded, placebo controlled trial to establish the efficacy and safety of favipiravir for mild Covid-19. We will enrol a total of 1400 participants, importantly including HIV-positive people, who will be followed up for 28 days post randomisation with a primary composite outcome of hospitalisation or death. This mutli-centre trial is a collaboration with the SAMRC and investigators at the University of Pretoria.