Covid-19 living Data

Camostat Mesilate vs Placebo (RCT)

Hospitalized patients

FOREST PLOTS -2022-10-20

Studies description

Trial NCT04321096 ; EudraCT Number: 2020001,20042
Publication Gunst J, EClinicalMedicine (2021) (published paper)
Dates: 2020-04-04 to 2020-12-31
Funding: Private (The Lundbeck Foundation)
Conflict of interest: Yes

Trial NCT04657497; jRCT2031200198
Publication CANDLE - Kinoshita T, BMC Medicine (2022) (published paper)
Dates: 2020-11-09 to 2021-03-30
Funding: Private (Ono Pharmaceutical Co., Ltd)
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / Japan Follow-up duration (days): 28
Inclusion criteria	Aged at least 18 years admitted to the participating hospitals within 5 days of onset of SARS-CoV-2 symptoms or within 5 days of a positive test for asymptomatic patients. SARS-CoV-2 infection must have been tested using a standard method at the time the study was conducted (e.g., reverse transcriptase-polymerase chain reaction [RT-PCR] test, loop-mediated isothermal amplification [LAMP] test, or antigen test) only patients with asymptomatic/mild or moderate infection provided informed consent.
Exclusion criteria	Severe infection, such as those requiring oxygenation, ventilation, or admission to an intensive care unit prior history of SARS-CoV-2 infection history of vaccination for SARS-CoV-2 history of treatment with camostat mesilate or nafamostat mesilate.
Interventions
	Treatment Camostat Mesilate 600 mg orally four times daily for up to 14 days.
	Control Placebo
Participants
	Randomized participants : Camostat Mesilate=78 Placebo=77
	Characteristics of participants N= 155 Mean age : NR 78 males Severity : Mild: n=108 / Moderate: n=0 / Severe: n=0 Critical: n=0
Primary outcome
	In the register Time to SARS-CoV-2 negative test [ Time Frame: Up to 14 days ]
	In the report Time to the first two consecutive negative SARS-CoV-2 tests
Documents avalaible	Protocol Yes. In English Statistical plan Yes 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 article, the prospective protocol, statistical analysis plan, supplementary appendix and prospective study registry were used in data extraction and risk of bias assessment. There is no change from the trial registration in the intervention and control treatments. The primary and secondary outcomes indicated in protocol and registry reflect the outcomes reported in the paper. The study (n=155) achieved the target sample size (n=110) specified in the protocol. On October 20tg, 2020, this study was updated with information extracted from the publication.

Methods
	RCT Blinding:
	Location : Multicenter / Denmark, Sweden Follow-up duration (days): 30
Inclusion criteria	Symptomatic Covid-19 infection PCR-positive for SARS-CoV-2 in respiratory tract samples hospital admission for ≤ 48 h.
Exclusion criteria	Serum total bilirubin ≥ 3 upper limit of normal range estimated glomerular filtration rate (eGFR) ≤30 mL/min pregnancy or breastfeeding unable to understand or sign the informed consent form (e.g. those requiring invasive mechanical ventilation at study entry).
Interventions
	Treatment Camostat Mesilate 200 mg three times a day for five days.
	Control Placebo
Participants
	Randomized participants : Camostat Mesilate=139 Placebo=69
	Characteristics of participants N= 208 Mean age : NR 123 males Severity : Mild: n=69 / Moderate: n=120 / Severe: n=16 Critical: n=0
Primary outcome
	In the register Clinical improvement defined as live hospital discharge OR a 2 point improvement (from time of enrolment) in disease severity rating on the 7-point ordinal scale.
	In the report Time to clinical improvement, defined as live hospital discharge or an improvement of at least 2 points from baseline on the 7-point ordinal scale, which ever came first
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication:
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 trial registry, protocol, statistical analysis plan (in the protocol) and supplementary files were used in data extraction and assessment of risk of bias. There were no substantive differences in population, procedures, or interventions between the published article and the trial registry, protocol and statistical analysis plan. The outcome 'Days in ICU' was specified in the trial protocol but not in the trial registry nor in the published paper. The article reports the inpatient part of a two-part trial that has two cohorts: one inpatients, one outpatients. The study achieved its pre-specified target sample size.