Molnupiravir versus favipiravir in at-risk outpatients with COVID-19: A randomized controlled trial in Thailand

• Published in: International Journal of Infectious Diseases
• Main Authors: Nicolas Salvadori, Gonzague Jourdain, Rungroj Krittayaphong, Taweegrit Siripongboonsitti, Subsai Kongsaengdao, Kriangsak Atipornwanich, Parichart Sakulkonkij, Nasikarn Angkasekwinai, Rujipas Sirijatuphat, Sarunyou Chusri, Tanavit Mekavuthikul, Anucha Apisarnthanarak, Sirawat Srichatrapimuk, Somnuek Sungkanuparph, Suppachok Kirdlarp, Thanyakamol Phongnarudech, Suraphan Sangsawang, Panuwat Napinkul, Jullapong Achalapong, Suwimon Khusuwan, Piyanut Pratipanawat, Pornboonya Nookeu, Namphol Danpipat, Pornvimol Leethong, Piya Hanvoravongchai, Pra-ornsuda Sukrakanchana, Prasert Auewarakul
• Format: Article
• Language: English
• Published: Elsevier 2024-06-01
• Subjects: Molnupiravir; Favipiravir; COVID-19; Outpatients; Randomized controlled trial; Thailand
• Online Access: http://www.sciencedirect.com/science/article/pii/S1201971224000924

Objectives: Evaluate and compare the efficacy and safety of molnupiravir and favipiravir in outpatients with mild to moderate COVID-19 and at risk of severe COVID-19. Methods: In an open-label, parallel-group, multicenter trial in Thailand, participants with moderate COVID-19 and at least one factor associated with severe COVID-19 were randomly assigned 1:1 to receive oral molnupiravir or oral favipiravir (standard of care). Phone calls for remote symptom assessment were made on Days 6, 15, and 29. Participants with worsening symptoms were instructed to return to the hospital. The primary endpoint was pulmonary involvement by Day 29, as evidenced by ≥2 of the following: dyspnea, oxygen saturation <92% or imaging. Results: Nine hundred seventy-seven participants (487 molnupiravir, 490 favipiravir) were enrolled from 8 July 2022 to 19 January 2023. 98% had received ≥1 dose of COVID-19 vaccine and 83% ≥3 doses. By Day 29, pulmonary involvement occurred in 0% (0/483) in molnupiravir arm versus 1% (5/482) in favipiravir arm (−1.0%; Newcombe 95.2% CI: −2.4% to −0.0%; P = 0.021); all-cause death in 0% (0/483) and <1% (1/482); COVID-19 related hospitalization in <1% (1/483) and 1% (3/482); treatment-related adverse event in 1% (5/483) and 1% (4/486); and serious adverse event in 1% (4/483) and 1% (4/486). Conclusions: Favipiravir and molnupiravir had a similar efficacy and safety profile. Whether either of the two reduced the risk of complications during the omicron era in this population with a low risk of pulmonary involvement and a high vaccine coverage remains unclear. There were no differences in any of the safety endpoints. Thai Clinical Trials Registry ID: TCTR20230111009.