Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial. Issue 10319 (1st January 2022)

• Record Type: Journal Article
• Authors: Ramacciotti, Eduardo; Barile Agati, Leandro; Calderaro, Daniela; Aguiar, Valéria Cristina Resende; Spyropoulos, Alex C; de Oliveira, Caroline Candida Carvalho; Lins dos Santos, Jessica; Volpiani, Giuliano Giova; Sobreira, Marcone Lima; Joviliano, Edwaldo Edner; Bohatch Júnior, Milton Sérgio; da Fonseca, Benedito Antônio Lopes; Ribeiro, Maurício Serra; Dusilek, Cesar; Itinose, Kengi; Sanches, Suzanna Maria Viana; de Almeida Araujo Ramos, Karine; de Moraes, Nara Franzin; Tierno, Paulo Fernando Guimarães Morando Marzocchi; de Oliveira, André Luiz Malavasi Longo; Tachibana, Adriano; Chate, Rodrigo Caruso; Santos, Marcus Vinícius Barbosa; de Menezes Cavalcante, Bruno Bezerra; Moreira, Ricardo Cesar Rocha; Chang, Chiann; Tafur, Alfonso; Fareed, Jawed; Lopes, Renato D; Benevenuto Caltabiano, Tania; Hattori, Breno; da Silva Jardim, Marcello; Marinho, Igor; Silva Marinho, Ivan; Mara Melo Batista, Liane; Rivabem, Lucas; Alberto Kenji Nakashima, Carlos; Carla Gois Franco, Ana; de Oliveira Pereira, Renata Fernanda; Strack Neves, Giana Caroline; de Castro e Souza, Izara; Moraes Ribas, Bruno; Ramos Tristão, Flavia; Barbosa Santos, Marcus Vinicius;
• Is Part Of: Lancet. Volume 399:Issue 10319(2022)
• Page Start: 50
• Page End: 59
• Publication Date: 2022-01-01
• Subjects: Medicine -- Periodicals; Medicine -- Periodicals; Medicine; Medicine; Electronic journals; Periodicals; 610.5
• DOI: 10.1016/S0140-6736(21)02392-8
• Languages: English
• ISSNs: 0140-6736

Abstract

Summary: Background: Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown. Methods: In this open-label, multicentre, randomised trial conducted at 14 centres in Brazil, patients hospitalised with COVID-19 at increased risk for venous thromboembolism (International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] venous thromboembolism [VTE] score of ≥4 or 2–3 with a D-dimer >500 ng/mL) were randomly assigned (1:1) to receive, at hospital discharge, rivaroxaban 10 mg/day or no anticoagulation for 35 days. The primary efficacy outcome in an intention-to-treat analysis was a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism on bilateral lower-limb venous ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism, and cardiovascular death at day 35. Adjudication was blinded. The primary safety outcome was major bleeding. The primary and safety analyses were carried out in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04662684 . Findings: From Oct 8, 2020, to June 29, 2021, 997 patients were screened. Of these patients, 677 did not meet eligibility criteria; the remaining 320 patients were enrolled and randomly assigned to receive rivaroxaban (n=160 [50%]) or no anticoagulation (n=160 [50%]). All patients received thromboprophylaxis with standard doses of heparin during hospitalisation. 165 (52%) patients were in the intensive care unit while hospitalised. 197 (62%) patients had an IMPROVE score of 2–3 and elevated D-dimer levels and 121 (38%) had a score of 4 or more. Two patients (one in each group) were lost to follow-up due to withdrawal of consent and not included in the intention-to-treat primary analysis. The primary efficacy outcome occurred in five (3%) of 159 patients assigned to rivaroxaban and 15 (9%) of 159 patients assigned to no anticoagulation (relative risk 0·33, 95% CI 0·12–0·90; p=0·0293). No major bleeding occurred in either study group. Allergic reactions occurred in two (1%) patients in the rivaroxaban group. Interpretation: In patients at high risk discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis. Funding: Bayer.