Table 2.

Clinical data available on the use of nafamostat mesylate in the treatment of COVID-19 patients

Authors	Location	Time when study was conducted	Type of study	Nafamostat dosing regimen	Participants	Outcomes	Adverse events reported
Iwasaka et al. [41]	Japan	February, 2020	Case series	0.2–0.4 mg/kg/h, in combination with hydroxychloroquine	1 elderly patient	Respiratory status and imaging results improved, and the patient was discharged from hospital	None reported
Jang and Rhee [39]	South Korea	February–March, 2020	Case series	200 mg for 24 h by continuous infusion in combination with lopinavir/ritonavir and hydroxychloroquine	3 elderly patients	All the patients showed radiological improvement and were discharged from the hospital	None reported
Hifumi et al. [42]	Japan	March–April, 2020	Case series	200 mg/day	1 adult patient	The patient recovered well	Diffuse microbleeding
Doi et al. [38]	Japan	April, 2020	Case series	0.2 mg/kg/h by continuous infusion, in combination with favipiravir	11 adult patients	7 (64%) successfully weaned from mechanical ventilation, 9 (82%) discharged from the ICU, 7 (64%) discharged from the hospital, 1 (9%) died	Hyperkalaemia 1 (9%)
Okajima et al. [25]	Japan	April, 2020	Case series	0.13–0.16 mg/kg/h	4 adult patients	4 (100%) developed hyperkalaemia immediately after nafamostat mesylate administration	Hyperkalaemia 4 (100%)
Takahashi et al. [40]	Japan	Not reported	Case series	200 mg/24 h, in combination with unfractioned heparin	1 elderly patient	The respiratory condition of the patient improved. Nafamostat-induced hyperkalaemia	Hyperkalaemia 1 (100%)
Koriyama et al. [43]	Japan	Not reported	Case series	100 mg daily in combination with dexamethasone	1 elderly patient	Fever reduction, decrease in D-dimer levers and oxygen administration discontinued. Patient was discharged	Not reported
Doi et al. [20]	Japan	October, 2020	Observational study	Doses according to disease severity (not specified) by continuous or intermittent infusion	515 adult patients	299 (58.1%) discharged alive, 52 (10.5%) transferred for de-escalation of care, 38 (7.4%) still hospitalised, 35 (6.8%) transferred for escalation of care, 89 (17.3%) died in hospital	Not reported
Inokuchi et al. [44]	Japan	January–December, 2020	Observational study	Not specified	15,859 adult patients (only 121 received nafamostat)	No difference in in-hospital mortality between the groups with nafamostat	Not reported
Zhuravel et al. [45]	Russia	September, November, 2020	Phase II, open-label, multicentre, randomised, controlled trial NCT04623021	4.8 mg/kg/day via 24-h intravenous infusion plus standard of care vs standard of care alone	102 adult patients	No significant difference in time to clinical improvement between the groups. No significant difference observed between the groups in the time of recovery. The observed benefits of nafamostat were more evident in patients with baseline NEWS ≥7. Secondary endpoints such as change in clinical status, shorter length of hospital stay, and 28-day mortality improved in the nafamostat group	Catheter site phlebitis 9 (8.8%) Hyponatremia 4 (3.9%) Respiratory failure 4 (3.9%)
Quinn et al. [28]	United Kingdom	September 2020–February 2021	Phase Ib/IIa, open-label, multicentre, platform, randomised, controlled trial ISRCTN14212905 NCT04473053 DEFINE trial	0.2 mg/kg/h by continuous infusion plus standard of care vs standard of care alone	42 adult patients	The nafamostat group had an average longer hospital stay and were on oxygen for a median of 2 days more than patients in the standard of care group. Nafamostat did not improve either the clinical biomarkers that show disease severity or the rate of change in any immune parameters	Hyperkalaemia 6 (14.3%)

COVID-19 coronavirus disease 2019, ICU intensive care unit, NEWS National Early Warning Score