tetano
Editor, Senior Moderator
Clin Infect Dis
. 2021 Sep 15;ciab813.
doi: 10.1093/cid/ciab813. Online ahead of print.
Randomized study of rivaroxaban vs. placebo on disease progression and symptoms resolution in high-risk adults with mild COVID-19
Jintanat Ananworanich[SUP] 1 [/SUP], Robin Mogg[SUP] 1 [/SUP], Michael W Dunne[SUP] 1 [/SUP], Mohamed Bassyouni[SUP] 1 [/SUP], Consuela Vera David[SUP] 2 [/SUP], Erika Gonzalez[SUP] 3 [/SUP], Taryn Rogalski-Salter[SUP] 1 [/SUP], Heather Shih[SUP] 1 [/SUP], Jared Silverman[SUP] 1 [/SUP], Jeroen Medema[SUP] 1 [/SUP], Penny Heaton[SUP] 1 [/SUP]
Affiliations
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.
Keywords: COVID; COVID-19; SARS-CoV-2; coronavirus; infection; pneumonia; rivaroxaban.
. 2021 Sep 15;ciab813.
doi: 10.1093/cid/ciab813. Online ahead of print.
Randomized study of rivaroxaban vs. placebo on disease progression and symptoms resolution in high-risk adults with mild COVID-19
Jintanat Ananworanich[SUP] 1 [/SUP], Robin Mogg[SUP] 1 [/SUP], Michael W Dunne[SUP] 1 [/SUP], Mohamed Bassyouni[SUP] 1 [/SUP], Consuela Vera David[SUP] 2 [/SUP], Erika Gonzalez[SUP] 3 [/SUP], Taryn Rogalski-Salter[SUP] 1 [/SUP], Heather Shih[SUP] 1 [/SUP], Jared Silverman[SUP] 1 [/SUP], Jeroen Medema[SUP] 1 [/SUP], Penny Heaton[SUP] 1 [/SUP]
Affiliations
- PMID: 34523673
- DOI: 10.1093/cid/ciab813
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.
Keywords: COVID; COVID-19; SARS-CoV-2; coronavirus; infection; pneumonia; rivaroxaban.