Association between Nafamostat Mesylate and In-Hospital Mortality in Patients with Coronavirus Disease 2019: A Multicenter Observational Study.

Ryota Inokuchi,Kazuaki Uda,Toshiki Kuno,Toshikazu Abe,Motohiko Adomi,Jun Komiyama,Nanako Tamiya,Yoshihisa Miyamoto,Masao Iwagami,Miho Ishimaru,Yuta Taniguchi

doi:10.3390/jcm11010116

Abstract

Nafamostat mesylate may be effective against coronavirus disease 2019 (COVID-19). However, it is not known whether its use is associated with reduced in-hospital mortality in clinical practice. We conducted a retrospective observational study to evaluate the effect of nafamostat mesylate in patients with COVID-19 using the Medical Data Vision Co. Ltd. hospital-based database in Japan. We compared patients with COVID-19 who were (n = 121) and were not (n = 15,738) administered nafamostat mesylate within 2 days of admission between January and December 2020. We conducted a 1:4 propensity score matching with multiple imputations for smoking status and body mass index and combined the 20 imputed propensity score-matched datasets to obtain the adjusted odds ratio for in-hospital mortality. Crude in-hospital mortality was 13.2% (16/121) and 5.0% (790/15,738), respectively. In the propensity score-matched analysis with multiple imputations, the adjusted odds ratio (use vs. no use of nafamostat mesylate) for in-hospital mortality was 1.27 (95% confidence interval: 0.61–2.64; p = 0.52). Sensitivity analyses showed similar results. The results of this retrospective observational study did not support an association between nafamostat mesylate and improved in-hospital outcomes in patients with COVID-19, although further studies with larger sample sizes are warranted to assess the generalizability of our findings.

Highlights

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
Nafamostat mesylate (NM) is a serine proteinase inhibitor that has been used in Japan for over 30 years to treat disseminated intravascular coagulation and pancreatitis [2]
We initially hypothesized that NM may improve patient outcomes, as experimental studies recently reported that NM inhibits the entry of SARS-CoV-2 into human epithelial cells [5,25], and several case reports have demonstrated the potential clinical benefits of NM [2,6–8]; we found no statistically significant association between NM and improvements in in-hospital mortality

Summary

Introduction

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Worldwide vaccination against SARS-CoV-2 is underway [1], it is imperative that researchers quickly identify suitable drugs for repurposing as COVID-19-specific therapies. Nafamostat mesylate (NM) is a serine proteinase inhibitor that has been used in Japan for over 30 years to treat disseminated intravascular coagulation and pancreatitis [2]. Experimental studies have shown that SARS-CoV-2 exerts an effect on human angiotensinconverting enzyme 2, enabling it to invade cells and establish infection [3]. In 293FT cells (derived from human fetal kidneys) that ectopically express angiotensin-converting enzyme. 2, NM prevents SARS-CoV-2 spike protein-initiated fusion by inhibiting protease [4]. It can be hypothesized that NM is effective against COVID-19

Objectives

Methods

Results