Clinical trial NCT00712101: Abciximab i.v. Versus i.c. in ST-elevation Myocardial Infarction
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: ST-elevation Myocardial Infarction
Keywords: infarction
intervention
stent
abciximab
platelets
Lead sponsor: University of Leipzig
Sponsor class: OTHER
First posted: 2008-07-09
Enrollment: 1912
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: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Clinical symptoms:

   * Angina pectoris \< 12 hours and
   * Persistent angina \> 30 minutes
2. 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
3. Informed consent

Exclusion Criteria:

1. No informed consent
2. Pregnancy
3. Known allergy to abciximab, ASA or heparin
4. Active peptic ulcus ventriculi or duodeni
5. Active, non-superficial bleeding
6. History of major surgery (including intracranial or intraspinal) \<4 weeks
7. active internal bleeding
8. Cerebrovascular complications \< 2 years
9. Known coagulation defect or thrombocytopenia
10. Arteriovenous malformations or aneurysm
11. Severe liver insufficiency, renal insufficiency requiring dialysis
12. Uncontrolled hypertension, hypertensive retinopathy
13. Vaskulitis
14. Thrombolysis \< 12 h
15. Participation in another trial

Primary outcomes:
measure: Combined clinical endpoint: death, reinfarction, new congestive heart failure
timeFrame: 90 days
Secondary outcomes:
measure: ST-segment resolution 90 minute ECG TIMI-flow post PCI indirect infarct size by enzyme release individual clinical endpoints
timeFrame: 90 days
Other outcomes:
Locations:
city: Bad Berka
country: Germany
facility: Zentralklinik Bad Berka
city: Bad Neustadt
country: Germany
facility: Herz- und Gefäß-KLinik Bad Neustadt
city: Bad Oeynhausen
country: Germany
facility: Herz und Diabeteszentrum Bad Oeynhausen
city: Bremen
country: Germany
facility: Klinikum Links der Weser - Bremen
city: Coburg
country: Germany
facility: Klinikum Coburg
city: Leipzig
country: Germany
facility: University of Leipzig - Heart Center
city: Merseburg
country: Germany
facility: Carl-von-Basedow-Klinikum Merseburg
city: Pirna
country: Germany
facility: Klinikum Pirna
city: Regensburg
country: Germany
facility: Krankenhaus der Barmherzigen Brüder
city: Ulm
country: Germany
facility: Jochen Wöhrle
city: Villingen-Schwenningen
country: Germany
facility: Klinikum der Stadt Villingen-Schwenningen
Study officials:
affiliation: Heart Center Leipzig - University Hospital
name: Holger Thiele, MD, PhD
role: STUDY_CHAIR
affiliation: Heart Center Leipzig - University Hospital
name: Gerhard Schuler, MD, PhD
role: STUDY_DIRECTOR
affiliation: University of Ulm
name: Jochen Woehrle, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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