1. Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III Clinical Trial
- Author
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Satoshi Iwata, Naoki Miyao, Takashi Naka, Takatomo Hirouchi, Atsushi Nakagawa, Yoshihiko Matsumoto, Yutaka Tokue, Jiro Terada, Kenji Tsushima, Kazutoshi Hiyama, Eri Hagiwara, Daiki Kanou, Shuichi Kawano, Tsutomu Sakurai, Yuko Komase, Yuji Hirai, Masahiro Shinoda, Shinichiro Ota, Mikio Takamori, Yoshitaka Yamazaki, Mitsunaga Iwata, Shingo Tanaka, Ichiro Kawada, Sho Fujiwara, Norihito Tarumoto, Kenya Ie, Shinichi Antoku, Naho Kagiyama, Megumi Shimada, Yujiro Uchida, Hiroyuki Kunishima, Osamu Kobayashi, Kazumasa Harada, Takeshi Saraya, Yasuhiro Gon, Yoshihiko Ogawa, Takashi Ogura, Masaharu Shinkai, and Hidefumi Koh
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,SARS-CoV-2 ,business.industry ,medicine.medical_treatment ,Phase III clinical trial ,COVID-19 ,Odds ratio ,Favipiravir ,Placebo ,medicine.disease ,Clinical trial ,Pneumonia ,Infectious Diseases ,Treatment efficacy ,Internal medicine ,Oxygen therapy ,medicine ,Clinical endpoint ,Moderate pneumonia not requiring oxygen therapy ,Oral antiviral agent ,business ,Adverse effect ,Original Research - Abstract
Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is an enveloped, single-stranded RNA virus. Favipiravir is an orally administrable antiviral drug whose mechanism of action is to selectively inhibit RNA-dependent RNA polymerase. A preliminary trial in COVID-19 patients reported significant improvements across a multitude of clinical parameters, but these findings have not been confirmed in an adequate well-controlled trial. We conducted a randomized, single-blind, placebo-controlled Phase III trial assessing the efficacy and safety of favipiravir in patients with moderate pneumonia not requiring oxygen therapy. Methods COVID-19 patients with moderate pneumonia (SpO2 ≥ 94%) within 10 days of onset of fever (temperature ≥ 37.5 °C) were assigned to receive either placebo or favipiravir (1800 mg twice a day on Day 1, followed by 800 mg twice a day for up to 13 days) in a ratio of 1:2. An adaptive design was used to re-estimate the sample size. The primary endpoint was a composite outcome defined as the time to improvement in temperature, oxygen saturation levels (SpO2), and findings on chest imaging, and recovery to SARS-CoV-2-negative. This endpoint was re-examined by the Central Committee under blinded conditions. Results A total of 156 patients were randomized. The median time of the primary endpoint was 11.9 days in the favipiravir group and 14.7 days in the placebo group, with a significant difference (p = 0.0136). Favipiravir-treated patients with known risk factors such as obesity or coexisting conditions provided better effects. Furthermore, patients with early-onset in the favipiravir group showed higher odds ratio. No deaths were documented. Although adverse events in the favipiravir group were predominantly transient, the incidence was significantly higher. Conclusions The results suggested favipiravir may be one of options for moderate COVID-19 pneumonia treatment. However, the risk of adverse events, including hyperuricemia, should be carefully considered. Trial registration Clinicaltrials.jp number: JapicCTI-205238. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00517-4.
- Published
- 2021