Supplementary Data — Ensitrelvir for COVID-19: real-time meta analysis of 7 studies

0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Mukae (DB RCT) 45% 0.55 [0.37-0.81] viral load 14 (n) 14 (n) Improvement, RR [CI] Treatment Control Mukae (DB RCT) 36% 0.64 [0.41-1.00] viral load 15 (n) 14 (n) Mukae (DB RCT) 45% 0.55 [0.34-0.90] viral time 15 (n) 14 (n) Mukae (DB RCT) 44% 0.56 [0.35-0.92] viral time 13 (n) 14 (n) Mukae (DB RCT) 54% 0.46 [0.05-4.38] viral+ 1/12 2/11 Mukae (DB RCT) -10% 1.10 [0.22-5.51] viral+ 3/15 2/11 Mukae (DB RCT) 80% 0.20 [0.01-3.80] viral+ 0/13 2/13 Mukae (DB RCT) 54% 0.46 [0.05-4.53] viral+ 1/14 2/13 Mukae (DB RCT) 54% 0.46 [0.10-2.12] viral+ 2/14 4/13 Mukae (DB RCT) 90% 0.10 [0.01-0.85] viral+ 0/15 4/13 Mukae (DB RCT) 80% 0.20 [0.05-0.75] viral+ 2/14 10/14 Mukae (DB RCT) 63% 0.37 [0.15-0.92] viral+ 4/15 10/14 Mukae (DB RCT) 9% 0.91 [0.59-1.40] viral+ 10/14 11/14 Mukae (DB RCT) -10% 1.10 [0.79-1.55] viral+ 13/15 11/14 Mukae (DB RCT) 9% 0.91 [0.76-1.08] improv. 116 (n) 111 (n) Mukae (DB RCT) 17% 0.83 [0.69-0.99] improv. 114 (n) 111 (n) Mukae (DB RCT) 32% 0.68 [0.56-0.82] viral time 113 (n) 108 (n) Mukae (DB RCT) 44% 0.56 [0.42-0.75] viral time 113 (n) 108 (n) SCORPIO-SR Yotsuyan.. (DB RCT) -1% 1.01 [0.06-16.1] hosp. 1/595 1/600 SCORPIO-SR Yotsuyan.. (DB RCT) 67% 0.33 [0.01-8.15] hosp. 0/603 1/600 SCORPIO-SR Yotsuyan.. (DB RCT) 11% 0.89 [0.71-1.11] recov. time 577 (n) 572 (n) SCORPIO-SR Yotsuyan.. (DB RCT) 10% 0.90 [0.68-1.19] recov. time 582 (n) 572 (n) SCORPIO-SR Yotsuyan.. (DB RCT) 18% 0.82 [0.67-1.00] recov. time 330 (n) 321 (n) SCORPIO-SR Yotsuyan.. (DB RCT) 19% 0.81 [0.67-0.98] recov. time 336 (n) 321 (n) SCORPIO-SR Yotsuyan.. (DB RCT) 13% 0.87 [0.65-1.17] recov. time 577 (n) 572 (n) SCORPIO-SR Yotsuyan.. (DB RCT) 10% 0.90 [0.49-1.68] recov. time 582 (n) 572 (n) SCORPIO-SR Yotsuyan.. (DB RCT) 13% 0.87 [0.74-1.02] recov. time 330 (n) 321 (n) SCORPIO-SR Yotsuyan.. (DB RCT) 16% 0.84 [0.70-1.01] recov. time 336 (n) 321 (n) SCORPIO-SR Yotsuyan.. (DB RCT) 49% 0.51 [0.34-0.76] viral load 579 (n) 589 (n) SCORPIO-SR Yotsuyan.. (DB RCT) 49% 0.51 [0.34-0.76] viral load 592 (n) 589 (n) SCORPIO-SR Yotsuyan.. (DB RCT) 59% 0.41 [0.24-0.69] viral load 330 (n) 321 (n) SCORPIO-SR Yotsuyan.. (DB RCT) 59% 0.41 [0.24-0.69] viral load 336 (n) 321 (n) Takazono (PSW) -24% 1.24 [0.17-9.05] death population-based cohort Takazono (PSW) -158% 2.58 [0.60-11.1] ventilation population-based cohort Takazono 97% 0.0 [0.00-4e+04] ICU population-based cohort Takazono (PSW) 36% 0.64 [0.26-1.56] oxygen population-based cohort Takazono (PSW) 37% 0.63 [0.42-0.94] hosp. population-based cohort SCORPIO-HR Luetkem.. (DB RCT) -203% 3.03 [0.32-29.1] hosp. 3/1,037 1/1,048 SCORPIO-HR Luetkem.. (DB RCT) 5% 0.95 [0.90-1.02] recov. time 945 (n) 943 (n) SCORPIO-HR Luetkem.. (DB RCT) 19% 0.81 [0.68-0.97] viral+ 175/882 215/881 SCORPIO-HR Luetkem.. (DB RCT) 16% 0.84 [0.77-0.91] viral+ 420/835 517/862 Katsuta 10% 0.90 [0.81-0.99] recov. time 60 (n) 42 (n) PLATCOV Schilling (RCT) 67% 0.33 [0.01-8.05] hosp. 0/197 1/191 PLATCOV Schilling (RCT) 3% 0.97 [0.14-6.81] hosp. 2/197 2/191 PLATCOV Schilling (RCT) 8% 0.92 [0.86-0.97] recov. time 197 (n) 191 (n) PLATCOV Schilling (RCT) 14% 0.86 [0.62-1.19] recov. time 197 (n) 191 (n) PLATCOV Schilling (RCT) 49% 0.51 [0.42-0.62] viral rate 201 (n) 191 (n) Ensitrelvir COVID-19 outcomes c19early.org November 2025 Favors ensitrelvir Favors control
Fig. S1. All outcomes.
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Fig. S2. Comparison of results for RCTs versus observational studies. For COVID-19 treatments, there is no significant difference between the results of RCTs and observational studies. Observational studies do not systematically over or underestimate efficacy. For high-cost treatments, there is a non-significant trend towards RCTs showing greater efficacy.