LV Thrombus After Acute AMI: A Randomized Controlled Trial

Sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other)

Overall Status

Unknown status

CT.gov ID

NCT01556659

Collaborator

VU University of Amsterdam (Other), Erasmus Medical Center (Other)

250

Enrollment

Location

Arms

Duration (Months)

6.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Ventricular Thrombosis Mural Following Myocardial Infarction	Drug: Absence of Acenocoumarol	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

250 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2012

Anticipated Primary Completion Date :

Dec 1, 2014

Anticipated Study Completion Date :

Jun 1, 2015

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

The proportions of patients with new cerebral micro-infarcts at 6 months relative to baseline measured by MRI. [6 months relative to baseline]
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.

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)