Covid-19 Living Data

Trial NCT04575038
Publication CRISIS2 - CRISIS2, Unpublished (2022) (results posted on registry)

Funding: Not reported/unclear
Conflict of interest: *

Methods
	RCT Blinding: quadruple blinding
	Location : Multicenter / USA Follow-up duration (days): 36
Inclusion criteria	Willing and able to provide informed consent for the trial, written, electronic, verbal or other method deemed acceptable by the institution and IRB 18 years of age or older Laboratory-confirmed SARS-CoV-2 infection as determined by real time polymerase chain reaction (RT-PCR) or other FDA-approved commercial or public health assay Out-patient (never hospitalized as an in-patient for COVID-19 or was evaluated/treated for COVID-19 only in the Emergency Room with a stay of < 24 hours) The effects of brequinar on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men and women treated or enrolled on this protocol must also agree to use adequate contraception for the duration of study participation, and for 90 days after completion of brequinar administration. Male subjects must agree to refrain from sperm donation and female subjects must agree to refrain from ovum donation from initial study drug administration until 90 days after the last dose of brequinar. Must have at least one COVID-19 symptom including but not limited to fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, shortness of breath, dyspnea, anosmia, dysgeusia, or other symptom commonly associated with COVID-19 in the opinion of the investigator. Symptom onset must be ≤7 days prior to first dose. Subject must have one or more symptoms at first dose Able to swallow capsules
Exclusion criteria	Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient Nursing women or women of childbearing potential (WOCBP) with a positive pregnancy test Treatment with another DHODH inhibitor (e.g., leflunomide, teriflunomide) or other agents known to cause bone marrow suppression leading to thrombocytopenia Platelets ≤150,000 cell/mm3 Hemoglobin < 10 gm/dL Absolute neutrophil count < 1500 cells/mm3 Renal dysfunction, i.e., creatinine clearance < 30 mL/min AST or ALT > 2 x ULN, or total bilirubin > ULN. Gilbert's Syndrome is allowed Bleeding disorders or blood loss requiring transfusion in the six weeks preceding enrollment Ongoing gastrointestinal ulcer, or gastrointestinal bleeding within 6 weeks of randomization Chronic hepatitis B infection, active hepatitis C infection, active liver disease and/or cirrhosis per subject report Heart failure, current uncontrolled cardiovascular disease, including unstable angina, uncontrolled arrhythmias, major adverse cardiac event within 6 months (e.g. stroke, myocardial infarction, hospitalization due to heart failure, or revascularization procedure)
Interventions
	Treatment Brequinar 100 mg orally once daily for 5 days
	Control Placebo
Participants
	Randomized participants : Brequinar=56 Placebo=59
	Characteristics of participants N= 115 Mean age : NR 56 males Severity : Mild: n= 104/ Asymptomatic: n=0 Number of vaccinated participants: NR
Primary outcome
	In the register Log10 SARS-CoV-2 Viral Load [ Time Frame: Days 4, 8, 12, 15, 22, and 29 ] Median Change from Baseline in Quantitative Log10 SARS-CoV-2 viral load at Days 4, 8, 12, 15, 22, and 29.
	In the report NR
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Not reported
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	Low
General comment	This is an unpublished trial whose results have been reported in ClinicalTrials.gov. The trial registry, protocol and statistical analysis plan were used in data extraction and assessment of risk of bias. The trial was registered prospectively and no important changes were made to primary or secondary outcomes after recruitment start. The trial (n = 115) achieved its target sample size (n = 100).