Antiviral effect and safety of nafamostat mesilate in patients with mild early-onset COVID-19: An exploratory multicentre randomized controlled clinical trial

Shu Okugawa; Mahoko Ikeda; Kosuke Kashiwabara; Takashi Moritoyo; Takao Kohsaka; Toshio Shimizu; Hideharu Hagiya; Kou Hasegawa; Fumio Otsuka; Ayumi Miwa; Nobuhito Kisimoto; Ayako Mizoguchi; Akira Imamura; Kazuhiko Ikeuchi; Takeya Tsutsumi; Daisuke Jubishi; Hideki Hashimoto; Koh Okamoto; Sohei Harada; Jun-Ichiro Inoue; Yasuyuki Seto; Kyoji Moriya

doi:10.1016/j.ijantimicag.2023.106922

Antiviral effect and safety of nafamostat mesilate in patients with mild early-onset COVID-19: An exploratory multicentre randomized controlled clinical trial

Int J Antimicrob Agents. 2023 Sep;62(3):106922. doi: 10.1016/j.ijantimicag.2023.106922. Epub 2023 Jul 8.

Authors

Shu Okugawa¹, Mahoko Ikeda², Kosuke Kashiwabara³, Takashi Moritoyo³, Takao Kohsaka⁴, Toshio Shimizu⁴, Hideharu Hagiya⁵, Kou Hasegawa⁵, Fumio Otsuka⁵, Ayumi Miwa⁶, Nobuhito Kisimoto⁷, Ayako Mizoguchi⁸, Akira Imamura⁹, Kazuhiko Ikeuchi¹⁰, Takeya Tsutsumi¹¹, Daisuke Jubishi¹, Hideki Hashimoto¹, Koh Okamoto¹, Sohei Harada¹², Jun-Ichiro Inoue¹³, Yasuyuki Seto¹⁴, Kyoji Moriya¹⁵

Affiliations

¹ Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan.
² Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan; Department of Infection Control and Prevention, The University of Tokyo Hospital, Tokyo, Japan.
³ Clinical Research Promotion Center, The University of Tokyo Hospital, Tokyo, Japan.
⁴ Department of Surgery, Horinouchi Hospital, Saitama, Japan.
⁵ Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
⁶ Pharmaceutical Department, Takamatsu Municipal Hospital, Kagawa, Japan.
⁷ Department of Pulmonary Medicine, Takamatsu Municipal Hospital, Kagawa, Japan.
⁸ Pharmaceutical Department, Moriya Keiyu Hospital, Ibaraki, Japan.
⁹ Department of Internal medicine, Moriya Keiyu Hospital, Ibaraki, Japan.
¹⁰ Division of Infectious Diseases, Advanced Clinical Research Center, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹¹ 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.
¹² Department of Infection Control and Prevention, The University of Tokyo Hospital, Tokyo, Japan.
¹³ The University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), Tokyo, Japan.
¹⁴ Department of Stomach and Esophageal Surgery, The University of Tokyo Hospital, Tokyo, Japan.
¹⁵ Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan; Department of Infection Control and Prevention, The University of Tokyo Hospital, Tokyo, Japan. Electronic address: moriyakyojl0720@gmail.com.

PMID: 37429450
DOI: 10.1016/j.ijantimicag.2023.106922

Abstract

Objectives: This study aimed to evaluate the antiviral effects and safety of nafamostat in early-onset patients with coronavirus disease 2019 (COVID-19).

Methods: In this exploratory multicentre randomized controlled trial, patients were assigned to three groups within 5 days of symptom onset, with 10 participants in each group: nafamostat at either 0.2 mg/kg/h or 0.1 mg/kg/h or a standard-of-care group. The primary endpoint was area under the curve for decrease in SARS-CoV-2 viral load in nasopharyngeal samples from baseline to day 6.

Results: Of the 30 randomized patients, 19 received nafamostat. Overall, 10 patients received low-dose nafamostat, 9 patients received high-dose nafamostat, and 10 received standard-of-care. The detected viruses were Omicron strains. The regression coefficient for area under the curve for decrease in viral load as the response variable and nafamostat dose per body weight as the explanatory variable showed a significant relationship of -40.1 (95% confidence interval, -74.1 to -6.2; P = 0.022). Serious adverse events were not observed in either group. Phlebitis occurred in ca. 50% of patients treated with nafamostat.

Conclusions: Nafamostat exerts virus load-reducing effects in patients with early-onset COVID-19.

Keywords: Nafamostat; SARS-CoV-2; TMPRSS2; Viral load.

Publication types

Randomized Controlled Trial
Multicenter Study

MeSH terms

Antiviral Agents / adverse effects
COVID-19*
Guanidines / adverse effects
Humans
SARS-CoV-2
Treatment Outcome

Substances

nafamostat
Antiviral Agents
Guanidines