REWARF-STEMI: Rivaroxaban vErsus Warfarin for Antithrombotic TheRapy in Patients With LeFt Ventricular Thrombus After Acute STEMI

Sponsor

Rajaie Cardiovascular Medical and Research Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05705089

Collaborator

Tehran Heart Center (Other)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to assess the safety and efficacy of rivaroxaban-based versus warfarin-based antithrombotic regimens on outcomes of patients with left ventricle thrombosis following acute ST elevation myocardial infarction at 3 months from enrollment in an open-label parallel groups pilot randomized clinical trial

Condition or Disease	Intervention/Treatment	Phase
Left Ventricular Thrombus ST Segment Elevation Myocardial Infarction	Drug: Rivaroxaban 15 MG Drug: Warfarin	Phase 3

Detailed Description

Direct oral anticoagulants (DOACs), are currently recognized as the first-line treatment of AF and VTE in most clinical scenarios, distinguished by their short half-life, fast onset of action, fewer medication interactions, rare food interactions, and the lack of a need for frequent laboratory monitoring, compared with vitamin K antagonists. Although the use of DOACs has earned a class III recommendation for patients with mechanical prosthetic valves, moderate-to-severe mitral stenosis, and antiphospholipid syndrome, their application in some situations, such as acute limb ischemia and LVT, remains uncertain. Until now, no completed randomized clinical trial has compared the efficacy and safety of left ventricle thrombosis in patients with acute STEMI and the existing evidence is limited to observational studies.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

1:1 open-label parallel group randomized controlled trial with concealed allocation sequence and blinded outcome adjudication1:1 open-label parallel group randomized controlled trial with concealed allocation sequence and blinded outcome adjudication

Masking:

Single (Outcomes Assessor)

Masking Description:

Allocation sequence concealment and blinded outcome adjudication

Primary Purpose:

Treatment

Official Title:

Rivaroxaban vErsus Warfarin for Antithrombotic TheRapy in Patients With LeFt Ventricular Thrombus After Acute ST-Elevation Myocardial Infarction: A Pilot Randomized Clinical Trial

Actual Study Start Date :

Jul 30, 2020

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rivaroxaban-based antithrombotic regimen All patients assigned to the rivaroxaban-based antithrombotic regimen will receive rivaroxaban (15 mg once daily, orally) plus clopidogrel (75 mg daily, orally) plus aspirin (80 mg once daily, orally). Aspirin will be discontinued within 7 days of its initiation. The antithrombotic regimen (i.e., dual therapy) will be continued until three months after randomization.	Drug: Rivaroxaban 15 MG Rivaroxaban 15 MG once daily orally + Dual anti-platelet therapy (clopidogrel (75 mg daily, orally)+aspirin (80 mg once daily, orally)) Other Names: XARELTO
Active Comparator: warfarin-based antithrombotic regimen All patients assigned to the warfarin-based antithrombotic regimen will receive warfarin (overlapping with enoxaparin until reaching an INR goal of 2-2.5) plus clopidogrel (75 mg once daily, orally) plus aspirin (80 mg once daily, orally). Aspirin will be discontinued within 7 days of its initiation. The antithrombotic regimen (i.e., dual therapy) will be continued until three months after randomization.	Drug: Warfarin Warfarin (to reach an INR goal of 2-2.5)+ Dual anti-platelet therapy (clopidogrel (75 mg daily, orally)+aspirin (80 mg once daily, orally))

Arm

Intervention/Treatment

Experimental: Rivaroxaban-based antithrombotic regimen

All patients assigned to the rivaroxaban-based antithrombotic regimen will receive rivaroxaban (15 mg once daily, orally) plus clopidogrel (75 mg daily, orally) plus aspirin (80 mg once daily, orally). Aspirin will be discontinued within 7 days of its initiation. The antithrombotic regimen (i.e., dual therapy) will be continued until three months after randomization.

Drug: Rivaroxaban 15 MG

Rivaroxaban 15 MG once daily orally + Dual anti-platelet therapy (clopidogrel (75 mg daily, orally)+aspirin (80 mg once daily, orally))

Other Names:

XARELTO

Active Comparator: warfarin-based antithrombotic regimen

All patients assigned to the warfarin-based antithrombotic regimen will receive warfarin (overlapping with enoxaparin until reaching an INR goal of 2-2.5) plus clopidogrel (75 mg once daily, orally) plus aspirin (80 mg once daily, orally). Aspirin will be discontinued within 7 days of its initiation. The antithrombotic regimen (i.e., dual therapy) will be continued until three months after randomization.

Drug: Warfarin

Warfarin (to reach an INR goal of 2-2.5)+ Dual anti-platelet therapy (clopidogrel (75 mg daily, orally)+aspirin (80 mg once daily, orally))

Outcome Measures

Primary Outcome Measures

Resolution of left ventricular thrombus [at 3 months from enrollment]
Resolution of left ventricular thrombus according to non-contrast 2D TTE performed by the imaging core laboratory, blinded to the allocation assignment

Other Outcome Measures

The proportion of patients with adjudicated stroke and systemic emboli [At 3 months from enrollment]
Stroke is defined as an acute episode of focal or global neurological dysfunction caused by the brain, spinal cord, or retinal vascular injury as a result of hemorrhage or infarction. Systemic emboli are defined as any acute non-cerebral embolic events with a cardiac origin.
The proportion of patients with adjudicated major adverse cardiac events (MACE) [At 3 months from enrollment]
A composite of death from cardiovascular causes, myocardial infarction, or stroke.
The proportion of patients with adjudicated all-cause death [At 3 months from enrollment]
All-cause death is defined as a composite of cardiovascular, non-cardiovascular and undetermined cause of death.
Left ventricular thrombus resolution percentage [At 3 months from enrollment]
Left ventricular thrombus resolution percentage according to non-contrast 2D TTE performed by the imaging core laboratory, blinded to the allocation assignment
The proportion of patients with adjudicated major bleeding events [At 3 months from enrollment]
Adjudicated based on International Society on Thrombosis and Hemostasis (ISTH) definition
The proportion of patients with adjudicated clinically relevant not major bleeding events [At 3 months from enrollment]
Adjudicated based on International Society on Thrombosis and Hemostasis (ISTH) definition

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria

Adult patients aged 18-80 years
Admission with acute STEMI in past 2 weeks
Acute LVT confirmed by non-contrast TTE
Willingness to participate and to provide a signed informed consent form

Exclusion criteria

History of the mechanical prosthetic heart valve, rheumatic heart disease, and confirmed case of antiphospholipid syndrome
Active bleeding
Cardiogenic shock defined as persistent hypotension (systolic blood pressure <90 mm Hg, or requirement of vasopressor to maintain systolic pressure >90 mm Hg) and clinical signs of hypoperfusion (cold, sweated extremities, oliguria, mental confusion, dizziness, narrow pulse pressure)
Acute kidney injury or chronic kidney disease with a glomerular filtration rate <30 ml/min (calculated based on the Cockcroft-Gault formula)
Liver failure (Child-Pugh class C)
Other indications for chronic anticoagulation (e.g., AF, VTE, etc.)
Sensitivity or intolerance to rivaroxaban/warfarin