International Journal of Infectious Diseases (Mar 2023)
Multicenter, single-blind, randomized controlled study of the efficacy and safety of favipiravir and nafamostat mesilate in patients with COVID-19 pneumonia
- Mahoko Ikeda,
- Shu Okugawa,
- Kosuke Kashiwabara,
- Takashi Moritoyo,
- Yoshiaki Kanno,
- Daisuke Jubishi,
- Hideki Hashimoto,
- Koh Okamoto,
- Kenji Tsushima,
- Yasuki Uchida,
- Takahiro Mitsumura,
- Hidetoshi Igari,
- Takeya Tsutsumi,
- Hideki Araoka,
- Kazuhiro Yatera,
- Yoshihiro Yamamoto,
- Yuki Nakamura,
- Amato Otani,
- Marie Yamashita,
- Yuji Wakimoto,
- Takayuki Shinohara,
- Maho Adachi-Katayama,
- Tatsunori Oyabu,
- Aoi Kanematsu,
- Sohei Harada,
- Yuichiro Takeshita,
- Yasutaka Nakano,
- Yasunari Miyazaki,
- Seiichiro Sakao,
- Makoto Saito,
- Sho Ogura,
- Kei Yamasaki,
- Hitoshi Kawasuji,
- Osamu Hataji,
- Jun-Ichiro Inoue,
- Yasuyuki Seto,
- Kyoji Moriya
Affiliations
- Mahoko Ikeda
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan; Department of Infection Control and Prevention, The University of Tokyo Hospital, Tokyo, Japan
- Shu Okugawa
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
- Kosuke Kashiwabara
- Clinical Research Promotion Center, The University of Tokyo Hospital, Tokyo, Japan
- Takashi Moritoyo
- Clinical Research Promotion Center, The University of Tokyo Hospital, Tokyo, Japan
- Yoshiaki Kanno
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
- Daisuke Jubishi
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
- Hideki Hashimoto
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
- Koh Okamoto
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
- Kenji Tsushima
- Department of Pulmonary Medicine, International University of Health and Welfare, Narita Hospital, Chiba, Japan
- Yasuki Uchida
- Division of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical Science, Shiga, Japan
- Takahiro Mitsumura
- Department of Respiratory Medicine, Tokyo Medical and Dental University Hospital, Tokyo, Japan
- Hidetoshi Igari
- Department of Infection Control, Chiba University Hospital, Chiba, Japan
- Takeya Tsutsumi
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan; Division of Infectious Diseases, Advanced Clinical Research Center, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Hideki Araoka
- Department of Infectious Diseases, Toranomon Hospital, Tokyo, Japan
- Kazuhiro Yatera
- Department of Respiratory Medicine, Hospital of the University of Occupational and Environmental Health, Fukuoka, Japan
- Yoshihiro Yamamoto
- Department of Clinical Infectious Diseases, Toyama University Hospital, Toyama, Japan
- Yuki Nakamura
- Respiratory Center, Matsusaka Municipal Hospital, Mie, Japan
- Amato Otani
- Research Platform Office, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Marie Yamashita
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
- Yuji Wakimoto
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
- Takayuki Shinohara
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
- Maho Adachi-Katayama
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
- Tatsunori Oyabu
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
- Aoi Kanematsu
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
- Sohei Harada
- Department of Infection Control and Prevention, The University of Tokyo Hospital, Tokyo, Japan
- Yuichiro Takeshita
- Department of Pulmonary Medicine, International University of Health and Welfare, Narita Hospital, Chiba, Japan
- Yasutaka Nakano
- Division of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical Science, Shiga, Japan
- Yasunari Miyazaki
- Department of Respiratory Medicine, Tokyo Medical and Dental University Hospital, Tokyo, Japan
- Seiichiro Sakao
- Department of Infection Control, Chiba University Hospital, Chiba, Japan
- Makoto Saito
- Division of Infectious Diseases, Advanced Clinical Research Center, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Sho Ogura
- Department of Infectious Diseases, Toranomon Hospital, Tokyo, Japan
- Kei Yamasaki
- Department of Respiratory Medicine, Hospital of the University of Occupational and Environmental Health, Fukuoka, Japan
- Hitoshi Kawasuji
- Department of Clinical Infectious Diseases, Toyama University Hospital, Toyama, Japan
- Osamu Hataji
- Respiratory Center, Matsusaka Municipal Hospital, Mie, Japan
- Jun-Ichiro Inoue
- Research Platform Office, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Yasuyuki Seto
- Department of Stomach and Esophageal Surgery, The University of Tokyo Hospital, Tokyo, Japan
- Kyoji Moriya
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan; Department of Infection Control and Prevention, The University of Tokyo Hospital, Tokyo, Japan; Corresponding author: Tel: +81-3-3815-5411.
- Journal volume & issue
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Vol. 128
pp. 355 – 363
Abstract
Objectives: To evaluate the efficacy and safety of nafamostat combined with favipiravir for the treatment of COVID-19. Methods: We conducted a multicenter, randomized, single-blind, placebo-controlled, parallel assignment study in hospitalized patients with mild-to-moderate COVID-19 pneumonia. Patients were randomly assigned to receive favipiravir alone (n = 24) or nafamostat with favipiravir (n = 21). The outcomes included changes in the World Health Organization clinical progression scale score, time to improvement in body temperature, and improvement in oxygen saturation (SpO2). Results: There was no significant difference in the changes in the clinical progression scale between nafamostat with favipiravir and favipiravir alone groups (median, -0.444 vs -0.150, respectively; least-squares mean difference, -0.294; P = 0.364). The time to improvement in body temperature was significantly shorter in the combination group (5.0 days; 95% confidence interval, 4.0-7.0) than in the favipiravir group (9.0 days; 95% confidence interval, 7.0-18.0; P =0.009). The changes in SpO2 were greater in the combination group than in the favipiravir group (0.526% vs -1.304%, respectively; least-squares mean difference, 1.831; P = 0.022). No serious adverse events or deaths were reported, but phlebitis occurred in 57.1% of the patients in the combination group. Conclusion: Although our study showed no differences in clinical progression, earlier defervescence, and recovery of SpO2 were observed in the combination group.
