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

Sponsor

Science Valley Research Institute (Other)

Overall Status

Completed

CT.gov ID

NCT04662684

Collaborator

Bayer (Industry)

320

Enrollment

Location

Arms

10.4

Actual Duration (Months)

30.6

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Covid19 Venous Thromboembolism	Drug: Rivaroxaban 10 MG	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

320 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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.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.

Masking:

None (Open Label)

Masking Description:

open-label

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Oct 16, 2020

Actual Primary Completion Date :

Jul 10, 2021

Actual Study Completion Date :

Aug 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rivaroxaban Rivaroxaban 10mg OD for 35+/- 4 days post-hospital discharge	Drug: Rivaroxaban 10 MG No intervention Other Names: No intervention
No Intervention: No intervention control

Arm

Intervention/Treatment

Experimental: Rivaroxaban

Rivaroxaban 10mg OD for 35+/- 4 days post-hospital discharge

Drug: Rivaroxaban 10 MG

No intervention

Other Names:

No intervention

No Intervention: No intervention

control

Outcome Measures

Primary Outcome Measures

Venous thromboembolism and VTE related-death [at day 35 +/- post hospital discharge]
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

Secondary Outcome Measures

Major bleeding [at day 35 +/- post hospital discharge]
Incidence of major bleeding according to ISTH criteria.

Other Outcome Measures

A composite of myocardial infarction, stroke, arrhythmias, heart failure, venous thromboembolism (VTE), and all-cause death. [at day 35 +/- post hospital discharge]
A composite of myocardial infarction, stroke, arrhythmias, heart failure, venous thromboembolism (VTE), and all-cause death.
Days alive out of the hospital (DAOH) at 35 +/-4 days [at day 35 +/- post hospital discharge]
Days alive out of the hospital (DAOH) at 35 +/-4 days
D-dimer (Biomarker) [at day 35 +/- 4 post hospital discharge]
plasma level of D-dimers in ng/mL
C reactive protein (Biomarker) [at day 35 +/- 4 post hospital discharge]
plasma level of C Reactive Protein in μg/mL

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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