Back to results

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

Primary Purpose

Covid19, Venous Thromboembolism

Status

Completed

Phase

Phase 3

Locations

Brazil

Study Type

Interventional

Intervention

Rivaroxaban 10 MG

About this trial

This is an interventional prevention trial for Covid19 focused on measuring Covid19, Venous Thromboembolism, Direct oral anticoagulants, Rivaroxaban

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Science Valley Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Rivaroxaban

No intervention

Arm Description

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

control

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Major bleeding

Incidence of major bleeding according to ISTH criteria.

Full Information

NCT ID

NCT04662684

First Posted

December 8, 2020

Last Updated

March 27, 2022

Sponsor

Science Valley Research Institute

Collaborators

Bayer

1. Study Identification

Unique Protocol Identification Number

NCT04662684

Brief Title

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

Acronym

MICHELLE

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Completed

Study Start Date

October 16, 2020 (Actual)

Primary Completion Date

July 10, 2021 (Actual)

Study Completion Date

August 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Science Valley Research Institute

Collaborators

Bayer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Covid19, Venous Thromboembolism

Keywords

Covid19, Venous Thromboembolism, Direct oral anticoagulants, Rivaroxaban

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

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.

Masking

None (Open Label)

Masking Description

open-label

Allocation

Randomized

Enrollment

320 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Rivaroxaban

Arm Type

Experimental

Arm Description

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

Arm Title

No intervention

Arm Type

No Intervention

Arm Description

control

Intervention Type

Drug

Intervention Name(s)

Rivaroxaban 10 MG

Other Intervention Name(s)

No intervention

Intervention Description

No intervention

Primary Outcome Measure Information:

Title

Venous thromboembolism and VTE related-death

Description

Time Frame

at day 35 +/- post hospital discharge

Secondary Outcome Measure Information:

Title

Major bleeding

Description

Incidence of major bleeding according to ISTH criteria.

Time Frame

at day 35 +/- post hospital discharge

Other Pre-specified Outcome Measures:

Title

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

Description

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

Time Frame

at day 35 +/- post hospital discharge

Title

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

Description

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

Time Frame

at day 35 +/- post hospital discharge

Title

D-dimer (Biomarker)

Description

plasma level of D-dimers in ng/mL

Time Frame

at day 35 +/- 4 post hospital discharge

Title

C reactive protein (Biomarker)

Description

plasma level of C Reactive Protein in μg/mL

Time Frame

at day 35 +/- 4 post hospital discharge

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Eduardo Ramacciotti, MD, Ph.D

Organizational Affiliation

Science Valley Research Institute

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Leandro Agati, PhD

Organizational Affiliation

Science Valley Research Institute

Official's Role

Study Director

Facility Information:

Facility Name

Science Valley Research Institute

City

Santo André

State/Province

São Paulo

ZIP/Postal Code

09030370

Country

Brazil

12. IPD Sharing Statement

Plan to Share IPD

Undecided

IPD Sharing Plan Description

Red Cap open file

Citations:

PubMed Identifier

34921756

Citation

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.

Results Reference

background

PubMed Identifier

34480880

Citation

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.

Results Reference

result

Learn more about this trial

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

We'll reach out to this number within 24 hrs