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

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, VTErelated death, VTE detected by bilateral lower limbs venous duplex scan and computed tomography pulmonary angiogram on day 35 +/- 4 posthospital discharge and symptomatic arterial thromboembolism (myocardial infarction, nonhemorrhagic stroke, major adverse limb events, and cardiovascular death) up to day 35 +/- 4 posthospital 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.