Summary of COVID-19 nafamostat studies

102 patient nafamostat late treatment RCT: 76% lower mortality (p=0.2), 42% greater improvement (p=0.28), and 42% improved recovery (p=0.28).
RCT 104 hospitalized patients with moderate to severe COVID-19 pneumonia showing no significant difference in the primary endpoint of time to clinical improvement with nafamostat. However, in patients with baseline National Early Warning Score (NEWS) ≥7, nafamostat treatment significantly shortened time to clinical improvement and recovery. Patients in the nafamostat group with NEWS ≥7 also had higher recovery rates and significantly reduced NEWS scores by day 11.
Nov 2021, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537021004491, https://c19p.org/zhuravelnf

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

29 patient nafamostat early treatment RCT: 33% improved viral clearance (p=0.007).
RCT 30 early-onset COVID-19 patients showing significantly improved viral load reduction with nafamostat.
Sep 2023, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857923002017, https://c19p.org/okugawanf

3. Morpeth et al., A Randomized Trial of Nafamostat for Covid-19

155 patient nafamostat late treatment RCT: 55% lower ventilation (p=0.23), 57% lower progression (p=0.14), and 28% improved recovery (p=0.36).
RCT 160 hospitalized non-critically ill COVID-19 patients showing a 93% posterior probability that nafamostat reduced the odds of death or receipt of ventilatory or vasopressor support by day 28 compared to usual care. Nafamostat, a TMPRSS2 inhibitor with potent in vitro antiviral activity against SARS-CoV-2, was administered as a continuous intravenous infusion for up to 7 days. The trial was conducted across 21 hospitals in Australia, New Zealand, and Nepal. Despite promising results, the trial was stopped early due to slowing recruitment, low event rates, and funding constraints, limiting definitive conclusions. Authors note that the posterior probability of effectiveness was higher among those with earlier disease onset, but lower during the Omicron era when variants were less dependent on the TMPRSS2 pathway.
Oct 2023, NEJM Evidence, https://evidence.nejm.org/doi/10.1056/EVIDoa2300132, https://c19p.org/morpethnf

4. Seccia et al., RAndomized Clinical Trial Of NAfamostat Mesylate, A Potent Transmembrane Protease Serine 2 (TMPRSS2) Inhibitor, in Patients with COVID-19 Pneumonia

14 patient nafamostat late treatment RCT: 67% lower mortality (p=1) and 20% improved recovery (p=1).
RCT 15 hospitalized COVID-19 patients showing a positive safety profile with nafamostat mesylate treatment. While the study was underpowered to detect differences in efficacy, Bayesian analysis suggested a signal for potential benefit (69-88% probability that nafamostat is effective depending on prior assumptions). Authors note that nafamostat, as a potent TMPRSS2 inhibitor with anticoagulant properties, could theoretically prevent virus entry into cells and complications like disseminated intravascular coagulation in COVID-19 patients. The study was significantly limited by small sample size due to recruitment challenges.
Oct 2023, J. Clinical Medicine, https://www.mdpi.com/2077-0383/12/20/6618, https://c19p.org/seccianf

5. Soma et al., Nafamostat Mesylate Monotherapy in Patients with Moderate COVID-19: a Single-Center, Retrospective Study

64 patient nafamostat late treatment study: 80% lower mortality (p=0.49) and 6% higher severe cases (p=1).
Retrospective 64 hospitalized patients with moderate COVID-19 showing no significant difference in clinical outcomes with nafamostat mesylate.
Sep 2022, Japanese J. Infectious Diseases, https://www.jstage.jst.go.jp/article/yoken/75/5/75_JJID.2021.699/_article, https://c19p.org/somanf

6. Quinn et al., Randomised controlled trial of intravenous nafamostat mesylate in COVID pneumonitis: Phase 1b/2a experimental study to investigate safety, Pharmacokinetics and Pharmacodynamics

42 patient nafamostat late treatment RCT: 48% longer hospitalization (p=0.21).
RCT 42 hospitalized patients with COVID-19 pneumonitis showing no benefit with intravenous nafamostat mesylate.
Feb 2022, eBioMedicine, https://www.sciencedirect.com/science/article/pii/S2352396422000408, https://c19p.org/quinnnf

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

15,859 patient nafamostat late treatment study: 27% higher mortality (p=0.52).
Retrospective multicenter observational study of 15,859 hospitalized COVID-19 patients in Japan showing no significant difference in in-hospital mortality with nafamostat mesylate. Very few patients received treatment and they had more severe disease on average. There may be significant residual confounding by indication.
Dec 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/11/1/116, https://c19p.org/inokuchi2nf

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