Efficacy of Early Treatment With Favipiravir on Disease Progression Among High-Risk Patients With Coronavirus Disease 2019 (COVID-19): A Randomized, Open-Label Clinical Trial
Authors: Chuah Chuan Huan , Chow Ting Soo , Hor Chee Peng , Cheng Joo Thye , Ker Hong Bee , Lee Heng Gee , Lee Kok Soon , Nordin Noridah , Ng Tiang Koi , Zaid Masliza , Zaidan Nor Zaila , Abdul Wahab Suhaila , Adnan Nurul Ashikin , Nordin Noorlina , Tee Tze Yuan , Ong Su Miin , Chidambaram Suresh Kumar , Mustafa Mahiran ,   Malaysian Favipiravir Study Group, Lee Kok Soon , Wong Chung Yeow , Sim Jian Hao , Yoong Nicholas Hee Ken , Tan Pei Sun , Peariasamy Kalaiarasu M , Ong Su Miin , Leong Chin Tho , Chew Chun Keat , Pathmanathan Mohan Dass , Hamzah Muhammad Luqman , Cheng Joo Thye , Hor Chee Peng , Abdullah Ammar Rashidi , Teoh Yee Jie , Lim Yi Fang , Zaidan Nor Zaila , Andu Delarina Frimawati Othman , Ajmera Divya Rajendra R , Singh Karamjit Kaur Sarban , Kamarudin Nurnadiah , Natarajan Peter Andrew , Tay Qin Le , Salim Seri Rabiatul Nur Abu , Vijayasingham Shalini , Kum Yik Zhi , Chow Ting Soo , Wong Peng Shyan , Leong Kar Nim , Chuah Chuan Huan , Ooi Bai Han , Bidin Farah Nadiah , Kang Kong Yeow , Chin Mann Leon , Lim Shiao Xian , Tan Shin Wuei , Mak Wen Yao , Chan Yeung Hsen , Lee Heng Gee , Tan Yee Ann , Saw Yen Tsen , Wong Yiko , Ker Hong Bee , Muniandy Balasurindiran , Guan Han Lin , Lim Chee Loon , Teing Pamela Saw Varn , Mustafa Mahiran , Nordin Noridah , Amiruddin Muhammad Aizat , Ahmad Raja Ahmad Reza Raja Lope , Mohammad Suhaili , Zaid Masliza , Ow Ji Ken , Sim Jian Hao , Lam Karin , Lee Kok Soon , Adnan Nurul Ashikin , Ab Rahman Ahmad Kashfi , Hanafi Mohd Haidi Syuhairi , Md Yusof Nurul Izza , Jamaluddin Wirdatul Ainna , Chidambaram Suresh Kumar , Shamsuddin Amira Naziffa , Chua Hiu Jian , George Isaac Heen , Tay Kim Heng , Tan Kok Tong , Narayanan Lavanya , Lim Kah Chuan , Subramaniam Nisshata , Hassan Nur Suriana Mah , Aik Pearly Sim Kim , Putra Raja Nurulain Raja Nahar , Nadzir Sharmila Mohd , Ain Syarifah Nurul , Ravi Tharmini a/p , Tan Yan Chyi , Tee Tze Yuan , Lee Foo Weng , Rajahram Giri Shan , Marzukie Marsilla Mariaty , Kerisnasamy Shivanessh , Wong Tzeng Lin , Nordin Noorlina , Chen Kah Mun , Mohamad Masyitah Haji , Hisham Muhammad Hazrul Badrul , Nik Ali Nik Fathanah , Lim Wai Tong , Wahab Suhaila Abdul , Anuar Amalina , Wong Chee Kong , Khalid Karniza , Ang Wei Chern , Ng Tiang Koi , Chong Chia Min , Chan Hui Ying , Suvintheran Thangavelu 
Published: November 2021

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).