Ensitrelvir for the Treatment of Hospitalized Adults With COVID-19: An International Phase 3 Randomized Placebo-controlled Trial

作者：Jason V. Baker, Lianne Siegel, Marcelo Losso, Shikha Vasudeva, Jacqueline Nordwall, Katrina Harper, Birgit Grund, Joshua P Havens, Courtney V. Fletcher, Roman Fishchuk, Olena Kobrynska, Akaki Abutidze, Revaz Metchurtchlishvili, Adit Ginde, Neil R. Aggarwal, Garyphiallia Poulakou, Ahmad Mourad, Kevin W. Gibbs, Sho Saito, Methee Chayakulkeeree, Piroon Mootsikapun, Hitoshi Honda, Lourdes Mateu, Olga Gyrina, Angie Garcia, D Lee, Jonathan D. Casey, Mamta K. Jain, Charles D. Bengtson, R Duncan Hite, Napon Hiranburana, Michael A. Matthay, Natalia Arizmendez, Hien Nguyen, Alexander Drelick, Alfredo J Mena Lora, Sam Parnia, Barbara W. Trautner, Simon Portsmouth, Ryosuke Shimizu, Takeki Uehara, Roger Paredes, Anna Goodman, David M. Vock, Annetine C. Gelijns, Amy Weintrob, Kristina L. Bajema, Sarah L Pett, Jens Lundgren, Adam Schechner, Elizabeth S. Higgs, H. Clifford Lane, Gail Matthews, Wesley H. Self, Cavan Reilly · 发表于：Clinical Infectious Diseases · 年份：2026 · DOI：10.1093/cid/ciag272 · 被引用次数：1 · 研究领域：COVID-19 Clinical Research Studies、Long-Term Effects of COVID-19、SARS-CoV-2 and COVID-19 Research

BACKGROUND: Antivirals remain an important treatment strategy for persons who experience severe and life-threatening COVID-19. Ensitrelvir is an oral 3CL protease inhibitor with potent antiviral activity. METHODS: We conducted an international randomized, placebo-controlled trial of ensitrelvir with standard of care (SOC) among adults hospitalized for COVID-19. The primary outcome was clinical recovery assessed by the days to recovery scale through day 60 (DRS-60), analyzed using a Van Elteren test. RESULTS: From 2023 to 2025, 589 participants received blinded study treatment (293 ensitrelvir and 296 placebo). Median age was 69 years, 49% were female, 68% were White, and SOC commonly included corticosteroids (61% and 54%) and remdesivir (62% and 60%) in ensitrelvir and placebo groups, respectively. Median DRS-60 category was 6 (IQR: 3-15) in the ensitrelvir and 5.5 (IQR: 3-12) in the placebo group (P = .19), and the OR was 0.82 (95% CI: 0.62-1.09) for a better DRS-60 category with ensitrelvir. Ensitrelvir participants had lower detectable viral antigen in plasma at Day 5 (13.4% vs 25.1%; P < .001). There was no difference in secondary clinical outcomes or prespecified safety outcomes, though the mortality rate was 6.1% vs 4.4% and the frequency of hemorrhagic events was 3.4% vs 0.3% among ensitrelvir and placebo groups, respectively. CONCLUSIONS: Ensitrelvir treatment did not improve clinical recovery in addition to SOC for adults hospitalized for COVID-19. The lower illness ...