Medically Ill hospitalized Patients for COVID-19 THrombosis Extended ProphyLaxis with rivaroxaban ThErapy: Rationale and Design of the MICHELLE Trial()

Ramacciotti, Eduardo; Agati, Leandro Barile; Calderaro, Daniela; Volpiani, Giuliano Giova; de Oliveira, Caroline Candida Carvalho; Aguiar, Valéria Cristina Resende; Rodrigues, Elizabeth; Sobreira, Marcone Lima; Joviliano, Edwaldo Edner; Dusilek, Cesar; Itinose, Kenji; Dedivitis, Rogério Aparecido; Cortina, André Sementilli; Sanches, Suzanna Maria Viana; 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; Cavalcante, Bruno Bezerra de Menezes; Moreira, Ricardo Cesar Rocha; Chiann, Chang; Tafur, Alfonso; Spyropoulos, Alex C.; Lopes, Renato D.

BACKGROUND: The devastating Coronavirus disease (COVID-19) pandemic is associated with a high prothrombotic state. It is unclear if the coagulation abnormalities occur because of the direct effect of SARS-CoV-2 or indirectly by the cytokine storm and endothelial damage or by a combination of mechanisms. There is a clear indication of in-hospital pharmacological thromboprophylaxis for every patient with COVID-19 after bleed risk assessment. However, there is much debate regarding the best dosage regimen, and there is no consensus on the role of extended thromboprophylaxis. DESIGN: This study aims to evaluate the safety and efficacy of rivaroxaban 10 mg once daily for 35±4 days versus no intervention after hospital discharge in COVID-19 patients who were at increased risk for VTE and have received standard parenteral VTE prophylaxis during hospitalization. The composite efficacy endpoint is a combination of symptomatic VTE, VTE-related death, VTE detected by bilateral lower limbs venous duplex scan and computed tomography pulmonary angiogram on day 35±4 post-hospital discharge and symptomatic arterial thromboembolism (myocardial infarction [MI], non-hemorrhagic stroke, major adverse limb events [MALE] and cardiovascular [CV] death) up to day 35±4 post-hospital discharge. The key safety outcome is the incidence of major bleeding according to ISTH criteria. SUMMARY: The MICHELLE trial is expected to provide high-quality evidence around the role of extended thromboprophylaxis in COVID-19 and will help guide medical decisions in clinical practice.