Randomized Study of Rivaroxaban vs Placebo on Disease Progression and Symptoms Resolution in High-Risk Adults With Mild Coronavirus Disease 2019.
COVID-19
SARS-CoV-2
infection
pneumonia
rivaroxaban
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
24 08 2022
24 08 2022
Historique:
received:
12
07
2021
pubmed:
16
9
2021
medline:
30
8
2022
entrez:
15
9
2021
Statut:
ppublish
Résumé
Severe acute respiratory syndrome coronavirus 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 coronavirus disease 2019 (COVID-19) progression. Adults (N = 497) with mild COVID-19 symptoms 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 end points were safety and progression. Absolute difference in progression risk was assessed using a stratified Miettinen and Nurminen method. The study was terminated after 497 of the target 600 participants were enrolled due to a prespecified interim analysis of the first 200 participants that crossed the futility boundary for the primary efficacy end point in the intent-to-treat population. Enrollees were 85% aged <65 years; 60% female; 27% Hispanic, Black, or other minorities; and 69% with ≥2 comorbidities. Rivaroxaban was well tolerated. Disease progression rates were 46 of 222 (20.7%) in rivaroxaban vs 44 of 222 (19.8%) in placebo groups, with a risk difference of -1.0 (95% confidence interval, -6.4 to 8.4; P = .78). We 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.
Sections du résumé
BACKGROUND
Severe acute respiratory syndrome coronavirus 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 coronavirus disease 2019 (COVID-19) progression.
METHODS
Adults (N = 497) with mild COVID-19 symptoms 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 end points were safety and progression. Absolute difference in progression risk was assessed using a stratified Miettinen and Nurminen method.
RESULTS
The study was terminated after 497 of the target 600 participants were enrolled due to a prespecified interim analysis of the first 200 participants that crossed the futility boundary for the primary efficacy end point in the intent-to-treat population. Enrollees were 85% aged <65 years; 60% female; 27% Hispanic, Black, or other minorities; and 69% with ≥2 comorbidities. Rivaroxaban was well tolerated. Disease progression rates were 46 of 222 (20.7%) in rivaroxaban vs 44 of 222 (19.8%) in placebo groups, with a risk difference of -1.0 (95% confidence interval, -6.4 to 8.4; P = .78).
CONCLUSIONS
We 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.
Identifiants
pubmed: 34523673
pii: 6370549
doi: 10.1093/cid/ciab813
pmc: PMC8522357
doi:
Substances chimiques
Rivaroxaban
9NDF7JZ4M3
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e473-e481Informations de copyright
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.
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