Chuan Huan Chuah1, Ting Soo Chow1, Chee Peng Hor2,3, Joo Thye Cheng4, Hong Bee Ker5, Heng Gee Lee6, Kok Soon Lee7, Noridah Nordin8, Tiang Koi Ng9, Masliza Zaid10, Nor Zaila Zaidan11, Suhaila Abdul Wahab12, Nurul Ashikin Adnan13, Noorlina Nordin14, Tze Yuan Tee15, Su Miin Ong16, Suresh Kumar Chidambaram17, Mahiran Mustafa8. 1. Department of Medicine, Penang General Hospital, Penang, Malaysia. 2. Department of Medicine, Kepala Batas Hospital, Penang, Malaysia. 3. Clinical Research Centre, Seberang Jaya Hospital, Penang, Malaysia. 4. Department of Medicine, Seberang Jaya Hospital, Penang, Malaysia. 5. Department of Medicine, Raja Permaisuri Bainun Hospital, Perak, Malaysia. 6. Department of Medicine, Queen Elizabeth Hospital, Sabah, Malaysia. 7. Department of Medicine, Enche' Besar Hajjah Khalsom Hospital, Johor, Malaysia. 8. Department of Medicine, Raja Perempuan Zainab II Hospital, Kelantan, Malaysia. 9. Department of Medicine, Tuanku Ja'afar Hospital, Negeri Sembilan, Malaysia. 10. Department of Medicine, Sultanah Aminah Hospital, Johor, Malaysia. 11. Department of Medicine, Melaka Hospital, Malacca, Malaysia. 12. Department of Medicine, Tuanku Fauziah Hospital, Perlis, Malaysia. 13. Department of Medicine, Sultanah Nur Zahirah Hospital, Terrengganu, Malaysia. 14. Department of Medicine, Tengku Ampuan Afzan Hospital, Pahang, Malaysia. 15. Department of Medicine, Tawau Hospital, Sabah, Malaysia. 16. Institute for Clinical Research, National Institutes of Health, Malaysia. 17. Department of Medicine, Sungai Buloh Hospital, Selangor, Malaysia.
Abstract
BACKGROUND: The role of favipiravir in preventing disease progression in coronavirus disease 2019 (COVID-19) remains uncertain. We aimed to determine its effect in preventing disease progression from nonhypoxia to hypoxia among high-risk COVID-19 patients. METHODS: This was an open-label, randomized clinical trial conducted at 14 public hospitals across Malaysia (February-July 2021) among 500 symptomatic, RT-PCR-confirmed COVID-19 patients, aged ≥50 years with ≥1 comorbidity, and hospitalized within first 7 days of illness. Patients were randomized 1:1 to favipiravir plus standard care or standard care alone. Favipiravir was administered at 1800 mg 2×/day on day 1 followed by 800 mg 2×/day until day 5. The primary endpoint was rate of clinical progression from nonhypoxia to hypoxia. Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, and in-hospital mortality. RESULTS: Of 500 patients randomized (mean [SD] age, 62.5 [8.0] years; 258 women [51.6%]; 251 [50.2%] had COVID-19 pneumonia), 487 (97.4%) patients completed the trial. Clinical progression to hypoxia occurred in 46 (18.4%) patients on favipiravir plus standard care and 37 (14.8%) on standard care alone (OR, 1.30; 95% CI: .81-2.09; P = .28). All 3 prespecified secondary endpoints were similar between both groups. Mechanical ventilation occurred in 6 (2.4%) vs 5 (2.0%) (OR, 1.20; 95% CI: .36-4.23; P = .76), ICU admission in 13 (5.2%) vs 12 (4.8%) (OR, 1.09; 95% CI: .48-2.47; P = .84), and in-hospital mortality in 5 (2.0%) vs 0 (OR, 12.54; 95% CI: .76-207.84; P = .08) patients. CONCLUSIONS: Among COVID-19 patients at high risk of disease progression, early treatment with oral favipiravir did not prevent their disease progression from nonhypoxia to hypoxia. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov (NCT04818320).
BACKGROUND: The role of favipiravir in preventing disease progression in coronavirus disease 2019 (COVID-19) remains uncertain. We aimed to determine its effect in preventing disease progression from nonhypoxia to hypoxia among high-risk COVID-19 patients. METHODS: This was an open-label, randomized clinical trial conducted at 14 public hospitals across Malaysia (February-July 2021) among 500 symptomatic, RT-PCR-confirmed COVID-19 patients, aged ≥50 years with ≥1 comorbidity, and hospitalized within first 7 days of illness. Patients were randomized 1:1 to favipiravir plus standard care or standard care alone. Favipiravir was administered at 1800 mg 2×/day on day 1 followed by 800 mg 2×/day until day 5. The primary endpoint was rate of clinical progression from nonhypoxia to hypoxia. Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, and in-hospital mortality. RESULTS: Of 500 patients randomized (mean [SD] age, 62.5 [8.0] years; 258 women [51.6%]; 251 [50.2%] had COVID-19 pneumonia), 487 (97.4%) patients completed the trial. Clinical progression to hypoxia occurred in 46 (18.4%) patients on favipiravir plus standard care and 37 (14.8%) on standard care alone (OR, 1.30; 95% CI: .81-2.09; P = .28). All 3 prespecified secondary endpoints were similar between both groups. Mechanical ventilation occurred in 6 (2.4%) vs 5 (2.0%) (OR, 1.20; 95% CI: .36-4.23; P = .76), ICU admission in 13 (5.2%) vs 12 (4.8%) (OR, 1.09; 95% CI: .48-2.47; P = .84), and in-hospital mortality in 5 (2.0%) vs 0 (OR, 12.54; 95% CI: .76-207.84; P = .08) patients. CONCLUSIONS: Among COVID-19 patients at high risk of disease progression, early treatment with oral favipiravir did not prevent their disease progression from nonhypoxia to hypoxia. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov (NCT04818320).