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

Covid19 Clinical Trial

— MICHELLE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04662684
• Other study ID #: 21589 Michelle Trial
• Status: Completed
• Phase: Phase 3
• Start date: October 16, 2020
• Est. completion date: August 30, 2021

Study information

• Verified date: March 2022
• Source: Science Valley Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 320
• Est. completion date: August 30, 2021
• Est. primary completion date: July 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19
• Thromboembolism
• Thrombosis
• Venous Thromboembolism

Intervention

Drug:
• Rivaroxaban 10 MG
No intervention

Locations

Country	Name	City	State
Brazil	Science Valley Research Institute	Santo André	São Paulo

Sponsors (2)

Lead Sponsor	Collaborator
Science Valley Research Institute	Bayer

Country where clinical trial is conducted

Brazil, 

References & Publications (2)

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, Santo — View 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 Júnior 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	at day 35 +/- post hospital discharge
Other	Days alive out of the hospital (DAOH) at 35 +/-4 days	Days alive out of the hospital (DAOH) at 35 +/-4 days	at day 35 +/- post hospital discharge
Other	D-dimer (Biomarker)	plasma level of D-dimers in ng/mL	at day 35 +/- 4 post hospital discharge
Other	C reactive protein (Biomarker)	plasma level of C Reactive Protein in µg/mL	at day 35 +/- 4 post hospital discharge
Primary	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	Major bleeding	Incidence of major bleeding according to ISTH criteria.	at day 35 +/- post hospital discharge