LV Thrombus After Acute AMI: A Randomized Controlled Trial

Left Ventricular Thrombus Formation After Acute Myocardial Infarction - a Randomized Multi-center Trial Comparing Two Different Anti-thrombotic Regimens

Left Ventricular (LV) thrombus formation is witnessed in at least 10% of patients with ST segment elevation myocardial infarction (STEMI). It is a feared complication since it might increase the risk of thrombo-embolic events, including stroke. Guidelines recommend vitamin K antagonist treatment in these patients. However patients with STEMI nowadays undergo primary percutaneous coronary intervention (PCI) with coronary stent placement and consequently require dual anti-platelet therapy (ascal and P2Y12 inhibitors) to prevent stent thrombosis. Consequently, STEMI patients with LV thrombus are currently treated with triple antithrombotic therapy (aspirin, P2Y12 inhibitors, e.g. clopidogrel (75 mg/d) and vitamin K antagonist). Patients treated with triple antithrombotic therapy are subject to a strongly increased bleeding risk with a yearly incidence of 3.7% for dual anti-platelet therapy as compared to 12% for triple antithrombotic therapy. About 10% of these bleedings are cerebral. The mortality of such haemorrhagic strokes is 25%. A recent retrospective analysis did not show any beneficial effects of addition of vitamin K antagonist to dual anti-platelet therapy to prevent stroke. If vitamin K antagonist-therapy could be omitted, morbidity and mortality due to post-PCI bleedings will decrease. Therefore, a randomized trial is warranted to address this issue.

Design: A multicenter, prospective, randomized, two non-inferiority trial. The objective of the study is to determine in a randomized fashion the risks and benefits of the addition of vitamin K antagonists to dual anti-platelet therapy or dual anti-platelet therapy in patients with PCI-treated STEMI and LV thrombus formation on baseline echocardiography or baseline Magnetic Resonance Imaging (MRI).

Study Overview

• Status: Unknown
• Conditions: Ventricular Thrombosis Mural Following Myocardial Infarction
• Intervention / Treatment: Drug: Absence of Acenocoumarol

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ronak Delewi, MD; Phone Number: +31 (0) 205666405; Email: r.delewi@amc.uva.nl
• Study Contact Backup: Name: Mariella Hassell, MD; Phone Number: +31 (0) 2056667883; Email: m.e.hassell@amc.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Recruiting
    • Academic Medical Center
    • Contact: Ronak Delewi, MD; Phone Number: +31 (0) 205666405; Email: r.delewi@amc.uva.nl
    • Contact: Mariella ECJ Hassell, MD; Phone Number: +31 (0) 2056667883; Email: m.e.hassell@amc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Suspected Left Ventricular thrombus on echocardiography or routine Magnetic Resonance Imaging
• Ongoing treatment with dual antiplatelet therapy according to ESC/ACC-AHA guidelines at the time of randomization.

Exclusion Criteria:

• Younger than 18
• Clinically or hemodynamically unstable
• Treatment with vitamin K antagonist prior to PCI or other expected indication for vitamin K antagonist treatment (e.g. atrium fibrillation) within the next 6 months
• Previous stroke or transient ischemic attack
• Scheduled for major surgery (including Coronary Artery Bypass Grafting) during the course of the study
• Active bleeding or high risk for bleeding contraindicating treatment with vitamin K antagonists
• Contra-indication for vitamin K antagonist treatment
• Chronic treatment with NSAIDs or COX-2 inhibitors for more than 4 days per week anticipated to continue during the study
• Congenital cardiac disease
• Presence of supraventricular or ventricular arrhythmias
• Expected candidate for ICD implantation with the next 6 months
• Severe renal impairment (estimated CrCl calculated by Cockcroft-Gault equation 5 30mL/min)
• Known or symptomatic brain disease (such as brain tumor)
• Women who are pregnant.
• Any contraindication for Contrast-Enhanced Magnetic Resonance Imaging (such as pacemaker, cerebrovascular clips, known contrast allergy, claustrophobia)
• Follow-up impossible (for example no fixed abode)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Triple antithrombotic therapy; Treatment with aspirin, P2Y12 inhibitors and vitamin K antagonist.	Drug: Absence of Acenocoumarol; Dual anti-platelet therapy without the addition of Acenocoumarol.
NO_INTERVENTION: Triple anti-thrombotic therapy; Treatment with aspirin, P2Y12 inhibitors and vitamin K antagonist.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportions of patients with new cerebral micro-infarcts at 6 months relative to baseline measured by MRI.	Primary outcome is defined as the proportions of patients with new cerebral micro-infarcts at 6 months relative to baseline measured by Magnetic Resonance Imaging.	6 months relative to baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
The presence of new cerebral micro-bleeds assessed by MRI	At 6 months and 12 months relative to baseline
Occurrence of major and minor bleeding	At 6 and 12 months relative to baseline
Neurological status	At 6 and 12 months relative to baseline
Quality of life.	At 6 and 12 months relative to baseline
Composite of vascular death, recurrent myocardial infarction, stroke or systemic embolism	At 6 and 12 months relative to baseline

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: Erasmus Medical Center; VU University of Amsterdam

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (ANTICIPATED): December 1, 2014
• Study Completion (ANTICIPATED): June 1, 2015

Study Registration Dates

• First Submitted: March 12, 2012
• First Submitted That Met QC Criteria: March 15, 2012
• First Posted (ESTIMATE): March 16, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): March 20, 2012
• Last Update Submitted That Met QC Criteria: March 19, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Anticoagulation; Acute myocardial infarction; Left ventricular thrombus
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Myocardial Infarction; Infarction; Thrombosis; Anticoagulants; Acenocoumarol
• Other Study ID Numbers: 2011-004265-32