medically ill hospitalized patients for covid-19 thrombosis extended prophylaxis with rivaroxaban therapy: the michelle trial

Conditions: Covid19; Venous Thromboembolism

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.

background: the devastating 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 vte prophylaxis. design: this study aims to evaluate the safety and efficacy of rivaroxaban 10 mg od 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, with a composite efficacy endpoint of symptomatic vte, vte-related death, and/or vte detected by mandatory bilateral lower limbs venous duplex scan and computed tomography pulmonary angiogram on day 35+/-4 post-hospital discharge. 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.

Eligibility criteria:
inclusion criteria: * male and nonpregnant female patients 18 years of age or older * positive reverse-transcriptase-polymerase-chain-reaction (rt-pcr) assay for sars-cov-2 in a respiratory tract sample * pneumonia confirmed by chest imaging * additional risk factors for vte, as indicated by a total modified international medical prevention registry on venous thromboembolism (improve) risk score of 4 or higher * have received thromboprophylaxis with low-molecular-weight heparin, fondaparinux, or unfractionated heparin during the index hospitalization exclusion criteria: * age \< 18 years * refusal of informed consent * physician decision that involvement in the trial was not in the patient's best interest * patients with a medical indication for anticoagulation therapy at the time of inclusion (for example, diagnosis of venous thromboembolism, atrial fibrillation, mechanical valve prosthesis) * platelets \< 50,000 / mm3 * patients with contraindications to anticoagulation (active bleeding, liver failure, blood dyscrasia, or prohibitive hemorrhagic risk in the investigator's assessment) * active cancer (excluding non-melanoma skin cancer) defined as cancer, not in remission or requiring active chemotherapy or adjunctive therapies such as immunotherapy or radiotherapy. * use of strong inhibitors of cytochrome p450 (cyp) 3a4 and/or glycoprotein p (p-gp) (eg protease inhibitors, ketoconazole, itraconazole) and/or use of p-gp and strong inducers of cyp3a4 (how but not limiting rifampicin/rifampicin, rifabutin, rifapentine, phenytoin, phenobarbital, carbamazepine or st. john's wort) * creatinine clearance \<30 ml / min * pregnancy or breastfeeding * known hiv infection * presence of one of the following uncontrolled or unstable cardiovascular diseases: stroke, ecg confirmed acute ischemia or myocardial infarction, and/or clinically significant dysrhythmia

Keywords: covid19 venous thromboembolism direct oral anticoagulants rivaroxaban