Covid-19 living Data

Nafamostat vs Standard care (RCT)

Hospitalized patients

FOREST PLOTS -2022-05-16

Studies description

Trial NCT04473053; ISRCTN14212905; EudraCT 2020-002230-3
Publication DEFINE - Quinn TM, EBioMedicine (2022) (published paper)
Dates: 2020-09-01 to 2021-02-28
Funding: Mixed (LifeArc and Oxford University COVID-19 Research Response Fund. Nichi-Iko (Japan) supplied Futhan (intravenous Nafamostat) for the trial.)
Conflict of interest: No

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / UK Follow-up duration (days): 131
Inclusion criteria	Over the age of 16 confirmed SARS-CoV-2 infection by RT-PCR chest radiographic changes consistent with COVID-19, or an additional oxygen requirement
Exclusion criteria	Pregnancy lactation inability to reliably take or tolerate modes of delivery of the treatment required anticoagulation, antiplatelet therapy or potassium sparing diuretics which could not reasonably be withheld current or recent history of severe uncontrolled cardiac disease, diabetes mellitus, renal impairment or hepatic impairment, anaemia, thrombocytopaenia, hyponatraemia or hyperkalaemia
Interventions
	Treatment Nafamostat 0.2 mg/kg/hr continuous infusion for 7 days
	Control Standard care
Participants
	Randomized participants : Nafamostat=23 Standard care=21
	Characteristics of participants N= 44 Mean age : NR 25 males Severity : Mild: n=0 / Moderate: n=* / Severe: n=* Critical: n=0
Primary outcome
	In the register 1) The safety of the candidate therapies in COVID-19 patients by measuring physiological changes in the circulatory and respiratory system. [ Time Frame: Up to 16 days post treatment ]; 2) The safety of the candidate therapies in COVID-19 patients by recording the number of treatment related adverse events. [ Time Frame: Up to 90 days post treatment ]
	In the report safety and tolerability of intravenous nafamostat as an add on therapy for patients hospitalised with COVID-19 pneumonitis.
Documents avalaible	Protocol Yes. In English Statistical plan NR Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the pre-print and published articles, the protocol and study registries were used in data extraction and risk of bias assessment. The primary outcomes in the article broadly reflect those in the registry. The two arms in the platform trial reported in the article along with a third unreported arm (n = 66 in total) appear not to have achieved the target sample size in the registry (n = 200). This study was updated on May 11th, 2022 with data extracted from the peer-reviewed report.

Trial NCT04623021
Publication Zhuravel SV, EClinicalMedicine (2021) (published paper)
Dates: 2020-09-25 to 2020-11-14
Funding: Mixed (Korea Research Institute of Bioscience and Biotechnology; Chong Kun Dang (CKD) Pharm (Seoul, Korea).)
Conflict of interest: Yes

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / Russia Follow-up duration (days): 28
Inclusion criteria	Hospitalised patients Aged ≥18 years Confirmed COVID-19 infection by RT-PCR of SARS-CoV-2 in a sample collected <72 hours prior to randomisation Newly diagnosed COVID-19 pneumonia by chest computed tomography (CT) scan or chest X-ray <72 hours prior to randomisation were enrolled Score of 4 (hospitalisation, requiring supplemental oxygen) or 5 (hospitalisation, requiring nasal high-flow oxygen therapy and/or non-invasive mechanical ventilation) using the 7-category ordinal scale for clinical status
Exclusion criteria	Requiring invasive mechanical ventilation and/or ECMO at screening Serious chronic disease with unstable disease status Active bleeding or any clinical condition deemed as high-risk for bleeding and a contraindication for anticoagulant treatment Pregnant or lactating females Hyperkalemia (serum potassium level >5.1 mmol/L) Moderate/severe liver disease (Child-Pugh score of B or C) ALT or AST levels >5-fold above the upper limit of normal (ULN) Estimated glomerular filtration rate (eGFR) <30 mL/min (including patients receiving hemodialysis or hemofiltration) Abnormal ECG (QTcB or QTcF >500 ms) Medical history of clinically significant ventricular arrhythmias Rapidly deteriorating clinical condition or low likelihood of completing the study according to the investigator's opinion Hypersensitivity to the investigational drug Clear evidence of secondary bacterial infection (diagnosed by laboratory tests and/or clinical examination)
Interventions
	Treatment Nafamostat 4.8 mg/kg/day intravenously for 10 days or until hospital discharge. Dose reduction was allowed by 0.1 mg/kg/hr (2.4 mg/kg/day) at the investigator's discretion as indicated by patient tolerability.
	Control Standard care
Participants
	Randomized participants : Nafamostat=53 Standard care=51
	Characteristics of participants N= 104 Mean age : NR 51 males Severity : Mild: n=0 / Moderate: n=94 / Severe: n=9 Critical: n=0
Primary outcome
	In the register Time to clinical improvement [ Time Frame: up to 28 days ] Time to clinical improvement (TTCI) was defined as time (days) from randomization to a decline of 2 categories on the seven-category ordinal scale of clinical status or live discharge from the hospital, whichever came first
	In the report Time to clinical improvement defined as the time from randomisation to either discharge from hospital or improvement of two points on the 7-category ordinal scale, whichever came first.
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the published article, the retrospective trial registry and supplementary appendices were used in data extraction and assessment of risk of bias. There is no information whether the sample size, outcomes or analysis plan were determined a-priori. The trial (n = 104) achieved the target sample size in the first version of the registry (n = 100).