Randomized Study of Rivaroxaban vs Placebo on Disease Progression and Symptoms Resolution in High-Risk Adults With Mild Coronavirus Disease 2019
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:75 |
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| Enthalten in: |
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America - 75(2022), 1 vom: 24. Aug., Seite e473-e481 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ananworanich, Jintanat [VerfasserIn] |
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| Links: |
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| Themen: |
9NDF7JZ4M3 |
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| Anmerkungen: |
Date Completed 29.08.2022 Date Revised 07.12.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/cid/ciab813 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM330657453 |
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| 245 | 1 | 0 | |a Randomized Study of Rivaroxaban vs Placebo on Disease Progression and Symptoms Resolution in High-Risk Adults With Mild Coronavirus Disease 2019 |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a infection | |
| 650 | 4 | |a pneumonia | |
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| 700 | 1 | |a Dunne, Michael W |e verfasserin |4 aut | |
| 700 | 1 | |a Bassyouni, Mohamed |e verfasserin |4 aut | |
| 700 | 1 | |a David, Consuela Vera |e verfasserin |4 aut | |
| 700 | 1 | |a Gonzalez, Erika |e verfasserin |4 aut | |
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| 700 | 1 | |a Medema, Jeroen |e verfasserin |4 aut | |
| 700 | 1 | |a Heaton, Penny |e verfasserin |4 aut | |
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