CompletedNCT04662684MICHELLEUpdated Apr 6, 2022

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

A Phase 3 interventional study of Rivaroxaban 10 MG in Covid19 and Venous Thromboembolism, sponsored by Science Valley Research Institute. Completed at 1 site in Brazil. Open to participants aged 18 Years to 90 Years. Per ClinicalTrials.gov, last updated 2022-04-06.

Sponsored by Science Valley Research Institute · Phase 3, Interventional, and Prevention

Phase: Phase 3
Study type: Interventional
Enrollment: 320
Allocation: Randomized
Ages: 18 Years to 90 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Covid19
Venous Thromboembolism

Browse trials for

Keywords

Covid19
Venous Thromboembolism
Direct oral anticoagulants
Rivaroxaban

In context

COVID-19

7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.

This study's enrollment of 320 is above the median of 100 across 4,099 interventional studies indexed under COVID-19.

Browse COVID-19 studies →

Lead sponsor

Science Valley Research Institute is the lead sponsor of 11 studies on the registry; 5 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 90 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Study design

Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 320 participants (actual)

Study arms

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

Interventions

DrugRivaroxaban 10 MG
No intervention
Also known as: No intervention

What researchers measure

Primary outcomes

Venous thromboembolism and VTE related-death
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
Time frame: at day 35 +/- post hospital discharge

Secondary outcomes

Major bleeding
Incidence of major bleeding according to ISTH criteria.
Time frame: at day 35 +/- post hospital discharge

Other outcomes

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

Study locations

1 site

Science Valley Research Institute
Santo André, São Paulo 09030370, Brazil

References and documents

Publications

Ramacciotti E, Barile Agati L, Calderaro D, Aguiar VCR, Spyropoulos AC, de Oliveira CCC, Lins Dos Santos J, Volpiani GG, Sobreira ML, Joviliano EE, Bohatch Junior MS, da Fonseca BAL, Ribeiro MS, Dusilek C, Itinose K, Sanches SMV, de Almeida Araujo Ramos K, de Moraes NF, Tierno PFGMM, de Oliveira ALML, Tachibana A, Chate RC, Santos MVB, de Menezes Cavalcante BB, Moreira RCR, Chang C, Tafur A, Fareed J, Lopes RD; MICHELLE investigators. Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial. Lancet. 2022 Jan 1;399(10319):50-59. doi: 10.1016/S0140-6736(21)02392-8. Epub 2021 Dec 15. PubMed 34921756 ↗
Ramacciotti E, Agati LB, Calderaro D, Volpiani GG, de Oliveira CCC, Aguiar VCR, Rodrigues E, Sobreira ML, Joviliano EE, Dusilek C, Itinose K, Dedivitis RA, Cortina AS, Sanches SMV, de Moraes NF, Tierno PFGMM, de Oliveira ALML, Tachibana A, Chate RC, Santos MVB, Cavalcante BBM, Moreira RCR, Chiann C, Tafur A, Spyropoulos AC, Lopes RD. Medically Ill hospitalized Patients for COVID-19 THrombosis Extended ProphyLaxis with rivaroxaban ThErapy: Rationale and Design of the MICHELLE Trial. Am Heart J. 2021 Dec;242:115-122. doi: 10.1016/j.ahj.2021.08.016. Epub 2021 Sep 1. PubMed 34480880 ↗

Individual participant data

Plan to share: Undecided — Red Cap open file

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 6, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04662684
Lead sponsor: Science Valley Research Institute
Collaborators: Bayer
Responsible party: Eduardo Ramacciotti (Principal Investigator, Science Valley Research Institute) — Principal investigator
First posted: Dec 10, 2020
Start date: Oct 16, 2020
Primary completion: Jul 10, 2021
Completion: Aug 30, 2021
Last update: Apr 6, 2022

Study contacts

Eduardo Ramacciotti, MD, Ph.D

study chair · Science Valley Research Institute

Leandro Agati, PhD

study director · Science Valley Research Institute

Oversight

Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2022. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

COVID-19→

Other studies from this sponsor

Science Valley Research Institute

Start the discussion