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

Myocardial Infarction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00133250
• Other study ID #: GE IDE No. I00902
• Status: Completed
• Phase: Phase 4
• First received: August 20, 2005
• Last updated: March 15, 2010
• Start date: June 2003
• Est. completion date: March 2008

Study information

• Verified date: March 2010
• Source: Deutsches Herzzentrum Muenchen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 800
• Est. completion date: March 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myocardial Infarction

Intervention

Drug:
• 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.

Other:
• 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.

Locations

Country	Name	City	State
Austria	Allgemeines Krankenhaus Wien	Vienna
Germany	Klinikum Garmisch-Partenkirchen	Garmisch-Partenkirchen
Germany	Deutsches Herzzentrum Muenchen	Munich
Germany	First Medizinische Klinik, Klinikum rechts der Isar	Munich
Germany	Klinikum Traunstein	Traunstein

Sponsors (2)

Lead Sponsor	Collaborator
Deutsches Herzzentrum Muenchen	Technische Universität München

Countries where clinical trial is conducted

Austria,  Germany, 

References & Publications (8)

Kastrati A, Mehilli J, Dirschinger J, Schricke U, Neverve J, Pache J, Martinoff S, Neumann FJ, Nekolla S, Blasini R, Seyfarth M, Schwaiger M, Schömig A; Stent versus Thrombolysis for Occluded Coronary Arteries in Patients With Acute Myocardial Infarction (STOPAMI-2) Study. Myocardial salvage after coronary stenting plus abciximab versus fibrinolysis plus abciximab in patients with acute myocardial infarction: a randomised trial. Lancet. 2002 Mar 16;359(9310):920-5. — View Citation

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, Schömig 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. — View Citation

Kastrati A, Mehilli J, Schühlen H, Dirschinger J, Dotzer F, ten Berg JM, Neumann FJ, Bollwein H, Volmer C, Gawaz M, Berger PB, Schömig 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. — View Citation

Mehilli J, Kastrati A, Schulz S, Früngel S, Nekolla SG, Moshage W, Dotzer F, Huber K, Pache J, Dirschinger J, Seyfarth M, Martinoff S, Schwaiger M, Schömig A; Bavarian Reperfusion Alternatives Evaluation-3 (BRAVE-3) Study Investigators. Abciximab in patie — View Citation

Müller I, Seyfarth M, Rüdiger S, Wolf B, Pogatsa-Murray G, Schömig A, Gawaz M. Effect of a high loading dose of clopidogrel on platelet function in patients undergoing coronary stent placement. Heart. 2001 Jan;85(1):92-3. — View Citation

Neumann FJ, Blasini R, Schmitt C, Alt E, Dirschinger J, Gawaz M, Kastrati A, Schömig A. Effect of glycoprotein IIb/IIIa receptor blockade on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction. Circulation. 1998 Dec 15;98(24):2695-701. — View Citation

Vermeer F, Oude Ophuis AJ, vd Berg EJ, Brunninkhuis LG, Werter CJ, Boehmer AG, Lousberg AH, Dassen WR, Bär FW. Prospective randomised comparison between thrombolysis, rescue PTCA, and primary PTCA in patients with extensive myocardial infarction admitted to a hospital without PTCA facilities: a safety and feasibility study. Heart. 1999 Oct;82(4):426-31. — View Citation

Weaver WD, Simes RJ, Betriu A, Grines CL, Zijlstra F, Garcia E, Grinfeld L, Gibbons RJ, Ribeiro EE, DeWood MA, Ribichini F. Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review. JAMA. 1997 Dec 17;278(23):2093-8. Erratum in: JAMA 1998 Jun 17;279(23):1876. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Left ventricular infarct size calculated as the final perfusion defect at follow-up scintigraphic study		5-7 days	No
Secondary	Clinical adverse events (death of any cause, reinfarction, stroke, urgent reinterventions, major and minor bleeding complications, thrombocytopenia <20 x 10^9 /L)		30 days	Yes