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

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

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

Study Overview

• Status: Completed
• Conditions: ST Segment Elevation Myocardial Infarction; Left Ventricular Thrombus
• Intervention / Treatment: Drug: Rivaroxaban 15 MG; Drug: Warfarin

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 Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 1995614331
    • Rajaie Cardiovascular Medical and Research Center
  • Tehran, Iran, Islamic Republic of
    • Tehran Heart Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

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

Exclusion criteria

1. History of the mechanical prosthetic heart valve, rheumatic heart disease, and confirmed case of antiphospholipid syndrome
2. Active bleeding
3. 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)
4. Acute kidney injury or chronic kidney disease with a glomerular filtration rate <30 ml/min (calculated based on the Cockcroft-Gault formula)
5. Liver failure (Child-Pugh class C)
6. Other indications for chronic anticoagulation (e.g., AF, VTE, etc.)
7. Sensitivity or intolerance to rivaroxaban/warfarin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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))

What is the study measuring?

Primary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients with adjudicated stroke and systemic emboli	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.	At 3 months from enrollment
The proportion of patients with adjudicated major adverse cardiac events (MACE)	A composite of death from cardiovascular causes, myocardial infarction, or stroke.	At 3 months from enrollment
The proportion of patients with adjudicated all-cause death	All-cause death is defined as a composite of cardiovascular, non-cardiovascular and undetermined cause of death.	At 3 months from enrollment
Left ventricular thrombus resolution percentage	Left ventricular thrombus resolution percentage according to non-contrast 2D TTE performed by the imaging core laboratory, blinded to the allocation assignment	At 3 months from enrollment
The proportion of patients with adjudicated major bleeding events	Adjudicated based on International Society on Thrombosis and Hemostasis (ISTH) definition	At 3 months from enrollment
The proportion of patients with adjudicated clinically relevant not major bleeding events	Adjudicated based on International Society on Thrombosis and Hemostasis (ISTH) definition	At 3 months from enrollment

Collaborators and Investigators

• Sponsor: Rajaie Cardiovascular Medical and Research Center
• Collaborators: Tehran Heart Center

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2020
• Primary Completion (Actual): February 1, 2023
• Study Completion (Actual): April 1, 2023

Study Registration Dates

• First Submitted: January 21, 2023
• First Submitted That Met QC Criteria: January 21, 2023
• First Posted (Actual): January 30, 2023

Study Record Updates

• Last Update Posted (Actual): April 7, 2023
• Last Update Submitted That Met QC Criteria: April 6, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: STEMI; Thrombosis; Blood Clot; Left Ventricle; Ventricle, Left; Thromboses; ST Segment Elevation Myocardial Infarction; ST Elevated Myocardial Infarction
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Thrombosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Warfarin
• Other Study ID Numbers: 20181022041406N4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No