Covid-19 Living Data

Trial NCT04504032
Publication Ananworanich J, Clin Infect Dis, 2021 (published paper)
Dates: 2020-08-16 to 2021-02-03
Funding: Public/non profit (Gates Philanthropy Partnerships, the Bill & Melinda Gates Foundation; Gates MRI (Medical writing).)
Conflict of interest: Yes

Methods
	RCT Blinding: triple blinding
	Location : Multicenter / USA Follow-up duration (days): 35
Inclusion criteria	≥18 years of age; documented positive SARs-CoV-2 polymerase chain reaction (PCR) test within 10 days of screening; at least one COVID-19 sign or symptom within 7 days of randomization; mild COVID-19 at screening; high risk for severe COVID-19 (either ≥65 years of age, diagnosed with a chronic disease requiring daily treatment (such as diabetes, lung disease, heart disease, hypertension or cancer), or self-reported obesity).
Exclusion criteria	Currently hospitalized or under immediate consideration for hospitalization at screening and Day 1; Have new onset shortness of breath or increased shortness of breath from pre-COVID-19 (for people with known COPD) at screening and Day 1; Hypoxemia (oxygen saturation<94% in ambient air or oxygen saturation below pre-COVID-19 oxygen saturation [if known] for people with known COPD) at Day 1; Require supplemental oxygen (new requirement or increase in requirement from pre-COVID-19 condition) at screening and Day 1; Have a history of (in the past 3 months) or current active pathological bleeding; Have a history of hemorrhagic stroke or intracranial hemorrhage ; Have a recent severe head trauma within 30 days which includes concussion, skull fracture or hospitalization for head injury; Have known intracranial neoplasm, cerebral metastases, arteriovenous malformation or aneurysm; Have history of pregnancy-related hemorrhage; Have active gastroduodenal ulcer or other gastrointestinal bleeding diagnosed in the past 3 months; Currently are in a hemodynamically unstable state; Currently require thrombolysis or pulmonary embolectomy; Have history of severe hypersensitivity reaction to Xarelto®; Currently have a prosthetic heart valve; Have known diagnosis of triple positive antiphospholipid syndrome; Have known diagnosis of chronic kidney disease (stage IV or receiving dialysis) ; Have a history of thrombocytopenia or known platelet count < 100,000 cells/mm3; Have a history of bronchiectasis and pulmonary cavitation; Have active cancer (eg, receiving chemotherapy or treatment for complication of the active cancer)
Interventions
	Treatment Rivaroxaban 10 mg orally once a day for 21 days
	Control Placebo
Participants
	Randomized 497 participants (n₁=246 / n₂= 251)
	Characteristics of participants N=497 Mean age : NR 177 males Severity : Mild: n=0 / Moderate: n=0/ Severe: n=0 Critical: n=0
Primary outcome
	In the register Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) [ Time Frame: Up to approximately 35 days ]; Number of Participants With AEs Leading to Study Discontinuation [ Time Frame: Up to approximately 35 days ]; Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Up to approximately 35 days ]; Proportion of Participants With Disease Progression [ Time Frame: Up to Day 28 ]
	In the report Safety: frequency of adverse events (AEs) including Grades 3 and 4, resulting in discontinuation, serious AEs and hypersensitivity and major bleeding events through Day 35. Efficacy: the proportion of participants who progressed to moderate or severe disease category (Gates MRI scale 3 or higher), through Day 28.
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated
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 and supplementary materials were used in data extraction and assessment of risk of bias. The primary and secondary endpoints in the article reflect those in the registry. The need to ship supplies to participants’ homes delayed time to first dose of study drug by about 2 days. Although a positive SARS-CoV-2 PCR, and symptomatic status were required at screening, by Day 1, 18% had a negative SARS-CoV-2 PCR and 0.7% were asymptomatic, and 4% had progressed to moderate or severe disease. Based on Data Monitoring Committee's recommendation on February 3, 2021, the study was stopped due to futility. The study was terminated after 497 of target 600 participants were enrolled.