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

NCT04662684 | Completed Phase 3 DMC

• 1 other identifier: 21589 Michelle Trial
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 1

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.

Conditions

Covid19; Venous Thromboembolism

Keywords

Covid19; Venous Thromboembolism; Direct oral anticoagulants; Rivaroxaban

Outcome Measures

Primary Outcomes (1)

• 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

  at day 35 +/- post hospital discharge

Secondary Outcomes (1)

• Major bleeding

  at day 35 +/- post hospital discharge

Other Outcomes (4)

• A composite of myocardial infarction, stroke, arrhythmias, heart failure, venous thromboembolism (VTE), and all-cause death.

  at day 35 +/- post hospital discharge

• Days alive out of the hospital (DAOH) at 35 +/-4 days

  at day 35 +/- post hospital discharge

• D-dimer (Biomarker)

  at day 35 +/- 4 post hospital discharge

Study Arms (2)

Rivaroxaban

EXPERIMENTAL

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

Drug: Rivaroxaban 10 MG

No intervention

NO INTERVENTION

control

Interventions

Rivaroxaban 10 MG DRUG

No intervention

Also known as: No intervention

Rivaroxaban

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Age \< 18 years
• Refusal of informed consent
• Physician decision that involvement in the trial was not in the patient's best interest
• 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

Sponsors & Collaborators

• Science Valley Research Institute: lead
• Bayer: collaborator

Study Sites (1)

Science Valley Research Institute

Santo André, São Paulo, 09030370, Brazil

Location

Related Publications (3)

• 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.

  PMID: 34921756 BACKGROUND

• 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.

  PMID: 34480880 RESULT

• Santos BC, Flumignan RL, Civile VT, Atallah AN, Nakano LC. Prophylactic anticoagulants for non-hospitalised people with COVID-19. Cochrane Database Syst Rev. 2023 Aug 16;8(8):CD015102. doi: 10.1002/14651858.CD015102.pub2.

  PMID: 37591523 DERIVED

MeSH Terms

Conditions

COVID-19; Venous Thromboembolism

Interventions

Rivaroxaban

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Eduardo Ramacciotti, MD, Ph.D

  Science Valley Research Institute

  STUDY CHAIR

• Leandro Agati, PhD

  Science Valley Research Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: open-label
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: December 8, 2020
• First Posted: December 10, 2020
• Study Start: October 16, 2020
• Primary Completion: July 10, 2021
• Study Completion: August 30, 2021
• Last Updated: April 6, 2022

Record last verified: 2022-03

Locations

BR (1)