Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID-19 (FACCT Trial): An Open-Label, Multicenter, Randomized, Controlled Trial
Mohammad Bosaeed, Ebrahim Mahmoud, Ahmad M. Alharbi, Hadeel Altayib, Hawra Albayat, Faisal Ghazi Alharbi, Khalid Ghalilah, Abdulmajid Al Arfaj, Jumana M. Al-Jishi, Abdullatif Alarfaj, Hajar AlQahtani, Badriah M. AlMutairi, Manar Almaghaslah, Nawaf M. Alyahya, Abdullah Bawazir, Saud Mohammed Saud Aleisa, Abdulrahman Alsaedy, Abderrezak Bouchama, Malak Alharbi, Majid M. Alshamrani, Sameera Al Johani, Majed Al-Jeraisy, Mohammed Alzahrani, Abdulhakeem Althaqafi, Hassan Almarhabi, Athari Alotaibi, Nasser Alqahtani, Yaseen M. Arabi, Omar Aldibasi, Ahmad Alaskar
Abstract
INTRODUCTION: Antiviral drugs have shown limited effectiveness in treating patients with coronavirus disease 2019 (COVID-19). We aimed to assess the effects of a favipiravir and hydroxychloroquine combination on treating moderate-to-severe COVID-19 patients. METHODS: ) of ≤ 94% while breathing ambient air or significant clinical symptoms with chest x-ray changes requiring hospital admission. Randomization was in a 1:1 ratio to receive standard care (control group) or standard care plus favipiravir and hydroxychloroquine. The primary outcome was time to clinical improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital within 14 days. Analyses were done in an intention-to-treat population. RESULTS: From May 2020 to Jan 2021, 254 patients were enrolled; 129 were assigned to standard of care and 125 to the treatment. The mean age was 52 (± 13) years, and 103 (41%) were women. At randomization, six patients were on invasive mechanical ventilation, 229 (90.15%) were requiring supplemental oxygen only (with or without non-invasive ventilation), and 19 (7.48%) were receiving neither. The time to clinical improvement was not significantly different between the groups: median of 9 days in the treatment group and 7 days in the control group (HR: 0.845; 95% CI 0.617-1.157; p-value = 0.29). The 28-day mortality was not significantly different between the groups (7.63% treatment) vs. (10.32% control); p-value = 0.45. The most prevalent adverse events were headache, elevation in ALT, and the prolonged QTc interval in the treatment group. CONCLUSION: The combination of favipiravir and hydroxychloroquine did not result in a statistically significant clinical benefit in patients with moderate-to-severe COVID-19. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04392973).