Medically Ill Hospitalized Patients for COVID-19 THrombosis Extended ProphyLaxis With Rivaroxaban ThErapy: The MICHELLE Trial

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