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LV Thrombus After Acute AMI: A Randomized Controlled Trial

Not Applicable
Terminated
Conditions
Ventricular Thrombosis Mural Following Myocardial Infarction
Interventions
Drug: Absence of vitamin K antagonist
Registration Number
NCT01556659
Lead Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
25
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
vitamin K antagonist -Absence of vitamin K antagonistTreatment with carbasalaatcalcium 100 mg/day, P2Y12 inhibitors (clopidogrel 1x 75mg, ticagrelor 2x 90 mg or prasugrel 1x 10mg/day)
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
The presence of new cerebral micro-bleeds assessed by MRIAt 6 months and 12 months relative to baseline
Occurrence of major and minor bleedingAt 6 and 12 months relative to baseline
Quality of life using a validated checklistAt 6 and 12 months relative to baseline
Neurological statusAt 6 and 12 months relative to baseline
Composite of vascular death, recurrent myocardial infarction, stroke or systemic embolismAt 6 and 12 months relative to baseline

Trial Locations

Locations (1)

Academic Medical Center

🇳🇱

Amsterdam, Netherlands

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