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
International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2023.106922
Objectives: This study aimed to evaluate the antiviral effects and safety of nafamostat in early-onset patients with coronavirus disease 2019 . 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.
Competing Interests: JI, YS, and KM are co-inventors on patent applications of nafamostat as an antiviral agent (PCT/JP2021/9968, patent applicant: the University of Tokyo). All other authors declare no competing interests. Towa Pharmaceutical Co., Ltd., supplied nafamostat mesilate. Ethical Approval: This study was approved by the Clinical Research Review Board of the University of Tokyo (approval number 2021501SP), and each participating hospital investigator received permission from their administrator to conduct the study. All participants provided written informed consent to participate in the study. The study was registered in the Japan Registry of Clinical Trials (jRCTs031210183).
Supplementary materials Supplementary material associated with this article can be found, in the online version, at doi: 10.1016/j.ijantimicag.2023. 106922 .
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