EClinicalMedicine (Jun 2023)

Rivaroxaban to prevent major clinical outcomes in non-hospitalised patients with COVID-19: the CARE – COALITION VIII randomised clinical trialResearch in context

  • Álvaro Avezum,
  • Haliton Alves Oliveira Junior,
  • Precil Diego M.M. Neves,
  • Lucas Bassolli O. Alves,
  • Alexandre B. Cavalcanti,
  • Regis G. Rosa,
  • Viviane C. Veiga,
  • Luciano C.P. Azevedo,
  • Sérgio Luiz Zimmermann,
  • Odilson Marcos Silvestre,
  • Raphael Cruz Seabra Prudente,
  • Adrian Paulo Morales Kormann,
  • Frederico Rafael Moreira,
  • Icaro Boszczowski,
  • Edgar de Brito Sobrinho,
  • André da Silva e Souza,
  • Renato Seligman,
  • Bruno de Souza Paolino,
  • Alvaro Razuk,
  • Audes Diogenes de Magalhaes Feitosa,
  • Pedro Luiz Monteiro Belmonte,
  • Priscila Freitas das Neves Gonçalves,
  • Mauro Esteves Hernandes,
  • Ariovaldo Leal Fagundes,
  • José Maria Sarmet Esteves,
  • Alexandre Pereira Tognon,
  • John Eikelboom,
  • Otávio Berwanger,
  • Renato D. Lopes,
  • Gustavo B.F. Oliveira

Journal volume & issue
Vol. 60
p. 102004

Abstract

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Summary: Background: COVID-19 progression is associated with an increased risk of arterial and venous thrombosis. Randomised trials have demonstrated that anticoagulants reduce the risk of thromboembolism in hospitalised patients with COVID-19, but a benefit of routine anticoagulation has not been demonstrated in the outpatient setting. Methods: We conducted a randomised, open-label, controlled, multicentre study, evaluating the use of rivaroxaban in mild or moderate COVID-19 patients. Adults ≥18 years old, with probable or confirmed SARS-CoV-2 infection, presenting within ≤7 days from symptom onset with no clear indication for hospitalization, plus at least 2 risk factors for complication, were randomised 1:1 either to rivaroxaban 10 mg OD for 14 days or to routine care. The primary efficacy endpoint was the composite of venous thromboembolic events, need of mechanical ventilation, acute myocardial infarction, stroke, acute limb ischemia, or death due to COVID-19 during the first 30 days. ClinicalTrials.gov: NCT04757857. Findings: Enrollment was prematurely stopped due to sustained reduction in new COVID-19 cases. From September 29th, 2020, through May 23rd, 2022, 660 patients were randomised (median age 61 [Q1-Q3 47–69], 55.7% women). There was no significant difference between rivaroxaban and control in the primary efficacy endpoint (4.3% [14/327] vs 5.8% [19/330], RR 0.74; 95% CI: 0.38–1.46). There was no major bleeding in the control group and 1 in the rivaroxaban group. Interpretation: On light of these findings no decision can be made about the utility of rivaroxaban to improve outcomes in outpatients with COVID-19. Metanalyses data provide no evidence of a benefit of anticoagulant prophylaxis in outpatients with COVID-19. These findings were the result of an underpowered study, therefore should be interpreted with caution. Funding: COALITION COVID-19 Brazil and Bayer S.A.

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