Randomized study of rivaroxaban vs. placebo on disease progression and symptoms resolution in high-risk adults with mild COVID-19

Bill & Melinda Gates Medical Research Institute, Cambridge, MA, USA. Science 37, Los Angeles, CA, USA. South Texas Allergy & Asthma Medical Professionals, San Antonio, TX, USA.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2021
PICO Summary

Population

Symptomatic adult patients with mild COVID-19 and at high-risk for COVID-19 progression (n= 497).

Intervention

Oral rivaroxaban (n= 246).

Comparison

Placebo-equivalent (n= 251).

Outcome

Rivaroxaban was well-tolerated. Disease progression rates were 46/222 (20.7%) in rivaroxaban vs. 44/222 (19.8%) in placebo groups, with a risk difference of -1.0.
Abstract
BACKGROUND SARS-CoV-2 infection may be associated with a prothrombotic state, predisposing patients for a progressive disease course. We investigated whether rivaroxaban, a direct oral anticoagulant factor Xa inhibitor would reduce COVID-19 progression. METHODS Adults (N=497) symptomatic with mild COVID-19 and at high-risk for COVID-19 progression based on age, body mass index, or comorbidity were randomized 1:1 to either daily oral rivaroxaban 10 mg (N=246) or placebo-equivalent (N=251) for 21 days and followed to Day 35. Primary endpoints were safety and progression to moderate or severe disease, per the Gates MRI scale. Absolute difference in progression risk was assessed using a stratified Miettinen and Nurminen method. RESULTS The study was terminated after 497 of target 600 participants were enrolled due to a pre-specified interim analysis of the first 200 participants which crossed the futility boundary for the primary efficacy endpoint in the Intent to Treat population. Enrollees were 85% aged < 65 years old, 60% female, 27% Hispanic, Black or other minorities and 69% with ≥2 comorbidities. Rivaroxaban was well-tolerated. Disease progression rates were 46/222 (20.7%) in rivaroxaban vs. 44/222 (19.8%) in placebo groups, with a risk difference of -1.0, 95% CI, -6.4 to 8.4; P = 0.78. CONCLUSIONS Our study did not demonstrate an impact of rivaroxaban on disease progression in high-risk adults with mild COVID-19. There remains a critical public health gap in identifying scalable effective therapies for high-risk people in the outpatient setting to prevent COVID-19 progression.
Study details
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine