Beyond 12 Hours Reperfusion AlternatiVe Evaluation Trial

NCT ID: NCT00759629

Last Updated: 2008-09-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 365 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-05-31
• Study Completion Date: 2005-08-31

Brief Summary

The objective of this international, multicenter, randomized study is to assess whether coronary artery stenting is associated with a reduced infarct size in patients with AMI presenting between 12 and 48 hours after onset of symptoms compared to medical treatment alone

Detailed Description

Between 8.5% and 40% of patients with acute myocardial infarction present late after symptom onset, no longer being eligible for thrombolysis.Despite efforts to reduce time to presentation, recent studies have demonstrated that time-to-arrival has not changed.The lack of efficacy of thrombolysis in patients with acute MI presenting > 12 hours after symptom onset may be a reason why current guidelines oppose reperfusion therapy in this setting.Several findings suggest, however,that reperfusion therapy may be beneficial even among these patients. First, recent studies have shown that viable salvageable myocardium exists even after >12 hours of severe ischemia. Second, previous studies have not only demonstrated that PCI is better than thrombolysis in patients with acute MI,but also that the time window of efficacy for PCI may be wider than that for thrombolysis.Third, observational studies suggest that PCI is effective even when performed after 12 hours from symptom onset in patients with acute MI. The goal of our trial was to assess whether an invasive strategy based on PCI with stenting is associated with reduction of infarct size in patients with acute STEMI presenting > 12 hours after symptom onset compared with a conventional conservative treatment strategy.

Conditions

Myocardial Infarction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

Interventional treatment group - Patients assigned to PCI will receive the loading dose of clopidogrel, aspirin plus a bolus of heparin and be transferred immediately for interventional treatment. They will receive abciximab as a bolus followed by a continuous infusion of for 12 hours.

Group Type: EXPERIMENTAL

Interventional treatment group

Intervention Type: OTHER

Patients assigned to PCI will receive the loading dose of clopidogrel (300 mg), 500 mg aspirin plus a bolus of 70 U/kg heparin i.v. and be transferred immediately for interventional treatment. They will receive abciximab as a bolus of 0.25 mg/Kg of body weight followed by a continuous infusion of 0.125 µg/Kg/minute (up to a maximal dose of 10 µg/minute) for 12 hours. All patients will undergo coronary angiography and left ventriculography in the conventional way. During the procedure patients will receive the weight-adjusted heparin doses (70 U/ kg). Post-procedural antithrombotic therapy will consist of clopidogrel in a daily dose of 75 mg for at least 4 weeks (6 months recommended) and aspirin, 100 mg to 350 mg daily, indefinitely.

B

Conservative treatment group - Patients assigned to this group will receive the usual therapy in the intensive care unit of the admitting hospital according to local standards.

Group Type: ACTIVE_COMPARATOR

Conservative treatment group

Intervention Type: OTHER

Patients assigned to this group will receive the usual therapy in the intensive care unit of the admitting hospital according to local standards. Per protocol, all patients in this arm will receive a loading dose of clopidogrel (300 mg) followed by 75 mg/day for at least 4 weeks (6 months recommended) after randomization and aspirin, indefinitely. Recommended additional regimen will include heparin, ß-blockers, ACE inhibitors and statins

Interventions

Interventional treatment group

Patients assigned to PCI will receive the loading dose of clopidogrel (300 mg), 500 mg aspirin plus a bolus of 70 U/kg heparin i.v. and be transferred immediately for interventional treatment. They will receive abciximab as a bolus of 0.25 mg/Kg of body weight followed by a continuous infusion of 0.125 µg/Kg/minute (up to a maximal dose of 10 µg/minute) for 12 hours. All patients will undergo coronary angiography and left ventriculography in the conventional way. During the procedure patients will receive the weight-adjusted heparin doses (70 U/ kg). Post-procedural antithrombotic therapy will consist of clopidogrel in a daily dose of 75 mg for at least 4 weeks (6 months recommended) and aspirin, 100 mg to 350 mg daily, indefinitely.

Intervention Type: OTHER

Conservative treatment group

Patients assigned to this group will receive the usual therapy in the intensive care unit of the admitting hospital according to local standards. Per protocol, all patients in this arm will receive a loading dose of clopidogrel (300 mg) followed by 75 mg/day for at least 4 weeks (6 months recommended) after randomization and aspirin, indefinitely. Recommended additional regimen will include heparin, ß-blockers, ACE inhibitors and statins

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• patients fulfilling the criteria of AMI and presenting at the hospital between 12 and 48 hours after onset of symptoms. The criteria of AMI are fulfilled when at least one episode of typical chest pain lasting ≥ 20 minutes is combined with either unequivocal ECG changes (≥ 0.1 mV of ST-segment elevation in ≥ 2 limb leads or ≥ 0.2 mV in ≥ 2 contiguous precordial leads or new pathological Q-waves) or CK plus concomitant CK-MB increase above twice the upper normal threshold. All patients have to be informed of the nature of the study and should give their informed consent for participation in the study.

Exclusion Criteria

• Age <18 years and > 80 years
• Cardiogenic shock (systolic blood pressure < 80 mm Hg unresponsive to fluids or necessitating the infusion of catecholamines: GUSTO I criteria)
• Persistent severe chest pain
• Prior thrombolysis (for index AMI)
• Malignancies with life expectancy < 1year
• History of bleeding diathesis, coagulopathy
• Contraindications to the antithrombotic therapy used in conjunction with coronary stenting (clopidogrel and abciximab)
• Stroke within the past 3 months
• Major surgery within the past 30 days
• Platelets < 100000/mm3 or >700000/mm3, Hb < 10g/dl, white blood cell count <3000/mm3
• Percutaneous coronary intervention within the past 30 days
• Inability to cooperate with study procedures and/or follow-up
• Previous enrollment in this trial

• 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 Schoemig, MD

Role: STUDY_CHAIR

Deutsches Herzzentrum Muenchen

Adnan Kastrati, MD

Role: PRINCIPAL_INVESTIGATOR

Deutsches Herzzentrum Muenchen

Locations

Landeskrankenhaus Feldkirch

Feldkirch, , Austria

Staedtisches Krankenhaus Bad Reichenhall

Bad Reichenhall, , Germany

Kreiskrankenhaus Erding/Dorfen

Erding, , Germany

Kreiskrankenhaus Freilassing

Freilassing, , Germany

Kreisklinik Fuerstenfeldbruck

Fürstenfeldbruck, , Germany

Klinikum Garmisch-Partenkirchen

Garmisch-Partenkirchen, , Germany

Deutsches Herzzentrum Muenchen

Munich, , Germany

1st Medizinische Klinik, Klinikum rechts der Isar

Munich, , Germany

Krankenhaus Vinzentinum Ruhpolding

Ruhpolding, , Germany

Krankenhaus Schongau

Schongau, , Germany

Klinikum Traunstein

Traunstein, , Germany

Kreisklinik Trostberg

Trostberg an der Alz, , Germany

Azienda Ospedaliera Careggi

Florence, , Italy

Ospedale, "Umberto I"

Mestre, , Italy

Countries

Austria; Germany; Italy

References

Schomig A, Mehilli J, Antoniucci D, Ndrepepa G, Markwardt C, Di Pede F, Nekolla SG, Schlotterbeck K, Schuhlen H, Pache J, Seyfarth M, Martinoff S, Benzer W, Schmitt C, Dirschinger J, Schwaiger M, Kastrati A; Beyond 12 hours Reperfusion AlternatiVe Evaluation (BRAVE-2) Trial Investigators. Mechanical reperfusion in patients with acute myocardial infarction presenting more than 12 hours from symptom onset: a randomized controlled trial. JAMA. 2005 Jun 15;293(23):2865-72. doi: 10.1001/jama.293.23.2865.

Reference Type: RESULT

PMID: 15956631 (View on PubMed)

Other Identifiers

GE IDE No. I00800

Identifier Type: -

Identifier Source: org_study_id