Clinical trial NCT01556659: LV Thrombus After Acute AMI: A Randomized Controlled Trial
Official title: Left Ventricular Thrombus Formation After Acute Myocardial Infarction - a Randomized Multi-center Trial Comparing Two Different Anti-thrombotic Regimens
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Ventricular Thrombosis Mural Following Myocardial Infarction
Keywords: Left ventricular thrombus
Acute myocardial infarction
Anticoagulation
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: VU University of Amsterdam
name: Erasmus Medical Center
First posted: 2012-03-16
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Detailed description: Design: A multicenter, prospective, randomized, non-inferiority trial with blinded evaluation of endpoints

Objective: The objective of this study is to determine in a randomized fashion the risks as well as the benefits of the addition of vitamin K antagonists to dual anti-platelet therapy in patients with PCI-treated STEMI and LV thrombus formation

Patients: Patients with acute myocardial infarction treated with primary PCI and LV thrombus on baseline echocardiography or baseline Magnetic Resonance Imaging. (MRI)

Methods: After written informed consent has been obtained, echocardiography and MRI are performed between 7-12 days after PCI. When LV thrombus is present on baseline MRI, patients are randomized to

1. Triple antithrombotic therapy (aspirin (100 mg/d), thienopyridine class antiplatelet agent,) and vitamin K antagonist (goal INR is 2.0 to 3.0))
2. Dual anti-platelet therapy (aspirin (100mg/d) and thienopyridine class antiplatelet agent, e.g. clopidogrel (75 mg/d).

Primary Endpoint: Primary outcome is defined as the proportions of patients with new cerebral micro-infarcts at 6 months relative to baseline measured by MRI.

Secondary Endpoints: The secondary endpoints as assessed at 6 and 12 months are:

* the composite of vascular death, recurrent myocardial infarction, stroke or systemic embolism
* presence of new cerebral mirco-bleeds
* the occurrence of major and minor bleeding
* neurological status and quality of life.

Eligibility criteria: 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)

Primary outcomes:
measure: The proportions of patients with new cerebral micro-infarcts at 6 months relative to baseline measured by MRI.
timeFrame: 6 months relative to baseline
Secondary outcomes:
measure: The presence of new cerebral micro-bleeds assessed by MRI
timeFrame: At 6 months and 12 months relative to baseline
measure: Occurrence of major and minor bleeding
timeFrame: At 6 and 12 months relative to baseline
measure: Neurological status
timeFrame: At 6 and 12 months relative to baseline
measure: Quality of life using a validated checklist
timeFrame: At 6 and 12 months relative to baseline
measure: Composite of vascular death, recurrent myocardial infarction, stroke or systemic embolism
timeFrame: At 6 and 12 months relative to baseline
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
Study officials:
affiliation: PI
name: Jan J Piek, Prof
role: PRINCIPAL_INVESTIGATOR
References: