Value of Abciximab in Patients With AMI Undergoing Primary PCI After Clopidogrel Pretreatment (BRAVE 3)

NCT ID: NCT00133250

Last Updated: 2010-03-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 800 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-30
• Study Completion Date: 2008-03-31

Brief Summary

The purpose of this study is to assess whether abciximab is associated with additional benefit in patients with AMI treated with PCI after high dose clopidogrel loading.

Detailed Description

The goal of all reperfusion therapies in acute myocardial infarction (AMI) is an effective restoration of coronary blood flow and the reduction of infarct size. Recently, the researchers were able to achieve excellent results with primary stenting plus abciximab in terms of reduction of infarct size and improvement of clinical outcome in the STOPAMI trial. This strategy provided a clear benefit compared to fibrinolysis. On the basis of the data published in the last 2 years, hospitals without angioplasty facilities have now better possibilities to improve the results of primary treatment of patients with AMI by immediately referring these patients to highly experienced centers in coronary interventions. There is an increasing interest to assess the additional advantages of pharmacologic reperfusion approaches which are readily applicable in the time window between presentation and arrival at the catheterization room. Two studies have shown that the results of the PCI in patients with AMI pretreated with fibrinolysis may even be more unfavorable than those achieved with angioplasty alone. Glycoprotein (GP) IIb/IIIa blocker abciximab has been shown to improve the results of the primary PCI in AMI. However, no rapidly effective antiplatelets therapy was available at the time when the studies on the benefit of abciximab were performed. Recent studies have shown that a high, 600 mg loading dose of clopidogrel is significantly more rapidly acting and that maximal inhibition of platelet aggregation is achieved within 2 hours after administration. In the ISAR-REACT trial, a high loading dose of clopidogrel was well tolerated, associated with such a low frequency of procedural complications that the use of abciximab offered no clinically measurable benefit at 30 days.

Comparison:

Abciximab (bolus+infusion for 12h) versus Placebo (bolus+infusion for 12h) after pre-treatment with 600 mg clopidogrel.

Conditions

Myocardial Infarction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

A

Abciximab

Group Type: EXPERIMENTAL

Abciximab

Intervention Type: DRUG

Abciximab bolus and infusion is given. Study medication includes 3 identical vials, each with 5 ml solution containing 10 mg abciximab. The bolus dose to be given should be rated at 0.125 ml/kg of patient's weight. After the bolus, a total dose of 0.045 ml/kg study substance (up to a maximal quantity of 3.6 ml) should be given over 12 hours.

B

Heparin Sodium

Group Type: PLACEBO_COMPARATOR

Placebo Heparin Sodium

Intervention Type: OTHER

Placebo bolus plus infusion is given. Study medication includes 3 identical vials, each with 5 ml solution containing 3000 U Heparin. The bolus dose to be given should be rated at 0.125 ml/kg of patient's weight. After the bolus, a total dose of 0.045 ml/kg study substance (up to a maximal quantity of 3.6 ml) should be given over 12 hours.

Interventions

Abciximab

Abciximab bolus and infusion is given. Study medication includes 3 identical vials, each with 5 ml solution containing 10 mg abciximab. The bolus dose to be given should be rated at 0.125 ml/kg of patient's weight. After the bolus, a total dose of 0.045 ml/kg study substance (up to a maximal quantity of 3.6 ml) should be given over 12 hours.

Intervention Type: DRUG

Placebo Heparin Sodium

Placebo bolus plus infusion is given. Study medication includes 3 identical vials, each with 5 ml solution containing 3000 U Heparin. The bolus dose to be given should be rated at 0.125 ml/kg of patient's weight. After the bolus, a total dose of 0.045 ml/kg study substance (up to a maximal quantity of 3.6 ml) should be given over 12 hours.

Intervention Type: OTHER

Other Intervention Names

ReoPro

Eligibility Criteria

Inclusion Criteria

• Patients presenting with ST-Elevation acute myocardial infarction within 24 hours from the onset of symptoms

Exclusion Criteria

• Age >80 years
• Malignancies
• Cardiogenic shock
• Prolonged cardio-pulmonary resuscitation
• Increased risk of bleeding
• Relevant hematologic deviations (hemoglobin <100 g/L or hematocrit <34%, platelet count <100 x 10^9 /L or platelet count >600 x 10^9 /L)
• Known allergy to the study medication
• Pregnancy (present or suspected)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Technical University of Munich

OTHER

Sponsor Role: collaborator

Deutsches Herzzentrum Muenchen

OTHER

Sponsor Role: lead

Responsible Party

Deutsches Herzzentrum Muenchen

Principal Investigators

Albert Schomig, MD

Role: STUDY_CHAIR

Deutsches Herzzentrum Muenchen

Adnan Kastrati, MD

Role: PRINCIPAL_INVESTIGATOR

Deutsches Herzzentrum Muenchen

Locations

Allgemeines Krankenhaus Wien

Vienna, , Austria

Klinikum Garmisch-Partenkirchen

Garmisch-Partenkirchen, , Germany

Deutsches Herzzentrum Muenchen

Munich, , Germany

First Medizinische Klinik, Klinikum rechts der Isar

Munich, , Germany

Klinikum Traunstein

Traunstein, , Germany

Countries

Austria; Germany

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 11119474 (View on PubMed)

Kastrati A, Mehilli J, Schlotterbeck K, Dotzer F, Dirschinger J, Schmitt C, Nekolla SG, Seyfarth M, Martinoff S, Markwardt C, Clermont G, Gerbig HW, Leiss J, Schwaiger M, Schomig A; Bavarian Reperfusion Alternatives Evaluation (BRAVE) Study Investigators. Early administration of reteplase plus abciximab vs abciximab alone in patients with acute myocardial infarction referred for percutaneous coronary intervention: a randomized controlled trial. JAMA. 2004 Feb 25;291(8):947-54. doi: 10.1001/jama.291.8.947.

Reference Type: BACKGROUND

PMID: 14982910 (View on PubMed)

Kastrati A, Mehilli J, Schuhlen H, Dirschinger J, Dotzer F, ten Berg JM, Neumann FJ, Bollwein H, Volmer C, Gawaz M, Berger PB, Schomig A; Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action for Coronary Treatment Study Investigators. A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel. N Engl J Med. 2004 Jan 15;350(3):232-8. doi: 10.1056/NEJMoa031859.

Reference Type: BACKGROUND

PMID: 14724302 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 11918909 (View on PubMed)

Mehilli J, Kastrati A, Schulz S, Frungel S, Nekolla SG, Moshage W, Dotzer F, Huber K, Pache J, Dirschinger J, Seyfarth M, Martinoff S, Schwaiger M, Schomig A; Bavarian Reperfusion Alternatives Evaluation-3 (BRAVE-3) Study Investigators. Abciximab in patients with acute ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention after clopidogrel loading: a randomized double-blind trial. Circulation. 2009 Apr 14;119(14):1933-40. doi: 10.1161/CIRCULATIONAHA.108.818617. Epub 2009 Mar 30.

Reference Type: RESULT

PMID: 19332467 (View on PubMed)

Schulz S, Birkmeier KA, Ndrepepa G, Moshage W, Dotzer F, Huber K, Dirschinger J, Seyfarth M, Schomig A, Kastrati A, Mehilli J. One-year clinical outcomes with abciximab in acute myocardial infarction: results of the BRAVE-3 randomized trial. Clin Res Cardiol. 2010 Dec;99(12):795-802. doi: 10.1007/s00392-010-0185-z. Epub 2010 Jun 27.

Reference Type: DERIVED

PMID: 20582594 (View on PubMed)

Other Identifiers

GE IDE No. I00902

Identifier Type: -

Identifier Source: org_study_id