Beyond 12 Hours Reperfusion AlternatiVe Evaluation Trial

Myocardial Infarction Clinical Trial

— Brave-2  

Official title:

An International, Multicenter, Randomized Trial Assessing the Value of Mechanical Reperfusion in Patients With Acute Myocardial Infarction Presenting > 12 Hours From Onset of Symptoms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00759629
• Other study ID #: GE IDE No. I00800
• Status: Completed
• Phase: Phase 4
• First received: September 24, 2008
• Last updated: September 24, 2008
• Start date: May 2001
• Est. completion date: August 2005

Study information

• Verified date: September 2008
• Source: Deutsches Herzzentrum Muenchen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 365
• Est. completion date: August 2005
• Est. primary completion date: January 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction

Intervention

Other:
• 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.
• 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

Locations

Country	Name	City	State
Austria	Landeskrankenhaus Feldkirch	Feldkirch
Germany	Staedtisches Krankenhaus Bad Reichenhall	Bad Reichenhall
Germany	Kreiskrankenhaus Erding/Dorfen	Erding
Germany	Kreiskrankenhaus Freilassing	Freilassing
Germany	Kreisklinik Fuerstenfeldbruck	Fuerstenfeldbruck
Germany	Klinikum Garmisch-Partenkirchen	Garmisch-Partenkirchen
Germany	1st Medizinische Klinik, Klinikum rechts der Isar	Munich
Germany	Deutsches Herzzentrum Muenchen	Munich
Germany	Krankenhaus Vinzentinum Ruhpolding	Ruhpolding
Germany	Krankenhaus Schongau	Schongau
Germany	Klinikum Traunstein	Traunstein
Germany	Kreisklinik Trostberg	Trostberg
Italy	Azienda Ospedaliera Careggi	Florence
Italy	Ospedale, "Umberto I"	Mestre

Sponsors (2)

Lead Sponsor	Collaborator
Deutsches Herzzentrum Muenchen	Technische Universität München

Countries where clinical trial is conducted

Austria,  Germany,  Italy, 

References & Publications (1)

Schömig A, Mehilli J, Antoniucci D, Ndrepepa G, Markwardt C, Di Pede F, Nekolla SG, Schlotterbeck K, Schühlen H, Pache J, Seyfarth M, Martinoff S, Benzer W, Schmitt C, Dirschinger J, Schwaiger M, Kastrati A; Beyond 12 hours Reperfusion AlternatiVe Evaluat — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint of the study is the infarct size calculated as the final perfusion defect (% of left ventricle) at the scintigraphic study		5-10 days	No
Secondary	Secondary endpoint of the study is the composite of all-cause death, recurrent MI, or stroke within 30 days after randomization.		30 days	Yes