Abciximab i.v. Versus i.c. in ST-elevation Myocardial Infarction

Study Overview
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Brief Summary
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The purpose of this study is to examine whether intracoronary abciximab bolus application with subsequent 12 hour intravenous infusion in addition to primary percutaneous coronary intervention is beneficial for patients with STEMI in comparison to standard i.v. bolus application with respect to 90-day mortality, reinfarction and new congestive heart failure.

Detailed Description
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In patients with acute ST-elevation myocardial infarction (STEMI) primary percutaneous coronary intervention (PCI) is the preferred reperfusion regimen, if performed by experienced operators in a timely manner. Nevertheless, myocardial damage is not immediately terminated after successful epicardial reperfusion by primary PCI. Current strategies are directed to improve myocardial tissue perfusion, which is impaired in approximately 50% of patients and which has prognostic impact. Adjunctive intravenous abciximab administration is an established therapy to improve coronary microcirculation and reduce major cardiac adverse events.5-10 In randomized clinical trials intravenous abciximab administration has been studied. Clinical trials have shown that earlier administration results in higher preinterventional TIMI-flow with subsequent improved perfusion post PCI. However, in a pooled analysis there was no effect on mortality. As door-to-balloon-times getting shorter in current trials, earlier abciximab administration requires treatment in the prehospital setting, which poses substantial logistic obstacles. Another option might be intracoronary abciximab bolus administration which results in very high local platelet inhibitor concentrations. This might be favorable in dissolution of thrombi and microemboli with subsequent improved myocardial microcirculation, reduction of no-reflow, and infarct size. Currently, there is only limited clinical experience on the efficacy of intracoronary abciximab administration mainly restricted to case reports, retrospective registries or small randomized trials. In a recently published randomized clinical trial, we were able to show that intracoronary versus intravenous abciximab bolus administration has beneficial effects on the occurrence of no-reflow and infarct size assessed by contrast-enhancement magnetic resonance imaging. This led to a trend towards improved clinical outcome. The composite major adverse cardiac event rate, defined as death, reinfarction, target vessel revascularization, and new congestive heart failure, at 30 day follow-up was 15.6% after intravenous and 5.2% after intracoronary abciximab administration (relative risk 3.00; 95% confidence intervals 0.94-10.80; p=0.06). Currently, there is no adequately powered clinical trial to assess the effects of intracoronary bolus in comparison to standard intravenous abciximab administration. Due to its general availability and its ease of intracoronary administration this treatment has overwhelming potential in clinical practice, which is much easier to achieve than a logistically cumbersome prehospital or interhospital transfer administration. In the era of evidence-based medicine, such a trial is of paramount importance to achieve a break-through in abciximab use and a reduction of the high associated morbidity and mortality of STEMI patients.

Official Title
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Prospective Randomized Controlled Clinical Study to Compare Abciximab-bolus i.v. Versus i.c. in Primary PCI in Patients With Acute ST-elevation Myocardial Infarction

Conditions
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ST-elevation Myocardial Infarction

Intervention / Treatment
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* Drug: abciximab intracoronary
* Drug: abciximab intravenously


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical symptoms: Angina pectoris < 12 hours and Persistent angina > 30 minutes ECG-criteria for ST-elevation myocardial infarction in 12-lead ECG: ST-segment elevation > 1mm in ≥ 2 extremity leads and/or ST-segment elevation > 2mm in ≥ 2 adjacent precordial leads Informed consent Exclusion Criteria: No informed consent Pregnancy Known allergy to abciximab, ASA or heparin Active peptic ulcus ventriculi or duodeni Active, non-superficial bleeding History of major surgery (including intracranial or intraspinal) <4 weeks active internal bleeding Cerebrovascular complications < 2 years Known coagulation defect or thrombocytopenia Arteriovenous malformations or aneurysm Severe liver insufficiency, renal insufficiency requiring dialysis Uncontrolled hypertension, hypertensive retinopathy Vaskulitis Thrombolysis < 12 h Participation in another trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Abciximab bolus administration intracoronary | Drug: abciximab intracoronary<br>* administer abciximab bolus intracoronary during primary percutaneous coronary intervention<br>|
| Active Comparator: 2<br>Abciximab bolus intravenously | Drug: abciximab intravenously<br>* administer abciximab bolus intravenously during primary percutaneous coronary intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined clinical endpoint: death, reinfarction, new congestive heart failure |  | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ST-segment resolution 90 minute ECG TIMI-flow post PCI indirect infarct size by enzyme release individual clinical endpoints |  | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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infarction, intervention, stent, abciximab, platelets