Clinical trial NCT00976092: Efficacy Study of Combined Prasugrel and Bivalirudin Versus Clopidogrel and Heparin in Myocardial Infarction
Official title: Randomized Trial of Prasugrel Plus Bivalirudin vs. Clopidogrel Plus Heparin in Patients With Acute STEMI
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Myocardial Infarction
Keywords: myocardial infarction
clopidogrel
prasugrel
bivalirudin
primary PCI
Lead sponsor: Deutsches Herzzentrum Muenchen
Sponsor class: OTHER
First posted: 2009-09-14
Enrollment: 548
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: Randomized comparison of two different anticoagulation strategies: prasugrel plus bivalirudin versus clopidogrel plus heparin in patients with acute myocardial infarction undergoing emergency catheterization and coronary intervention.

Detailed description: Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion strategy for patients with acute ST-segment elevation myocardial infarction (STEMI). Additional anticoagulation therapy prior or during intervention plays an important role in the short- and long-term outcomes after PPCI. Two separate studies have shown significant benefit against conventional therapy based on clopidogrel and heparin for two recently approved drugs: the direct thrombin inhibitor bivalirudin and the thienopyridine prasugrel. In the HORIZONS-AMI trial, bivalirudin after pretreatment with clopidogrel resulted in improved net clinical outcomes. However, during the first 24 hours after PPCI an increase in the stent thrombosis rate was observed with bivalirudin therapy. Prasugrel has been shown to be superior to clopidogrel in patients with acute coronary syndromes undergoing PCI. The benefit in reduction of ischemic complication was even greater in the subset of patients with STEMI without any increase in the bleeding risk and with a significant reduction in the stent thrombosis rate. Expectedly, the synergic actions of prasugrel and bivalirudin may maximize the benefit of antithrombotic therapy for STEMI patients undergoing PPCI.

Eligibility criteria: Inclusion Criteria:

1. Patients presenting within 24 hours from the onset of symptoms with STEMI
2. Informed, written consent
3. In women with childbearing potential a pregnancy test is obligatory.

Exclusion Criteria:

1. Age \< 18 years
2. Cardiogenic shock
3. Active bleeding; bleeding diathesis; coagulopathy
4. History of gastrointestinal or genitourinary bleeding \<2 months
5. Refusal to receive blood transfusion
6. Major surgery in the last 6 weeks
7. History of intracranial bleeding or structural abnormalities
8. Suspected aortic dissection
9. Heparin-induced thrombocytopenia
10. Any previous stroke
11. Prior administration of thrombolytics, bivalirudin, low-molecular weight heparin or fondaparinux for the index MI
12. Known relevant hematological deviations: Hb \<100g/l, Thromb. \<100x10\^9/l
13. Use of coumadin derivatives within the last 7 days
14. Chronic therapy with nonsteroidal anti-inflammatory drugs (except aspirin), COX-2 inhibitors, prasugrel
15. Known malignancies or other comorbid conditions with life expectancy \<1 year
16. Known severe liver disease, severe renal failure
17. Known allergy to the study medications
18. Previous enrollment in this trial
19. Pregnancy

Primary outcomes:
measure: composite of all-cause death, recurrent MI, unplanned IRA revascularization, stroke, definite stent thrombosis or major bleeding
timeFrame: 30 days
Secondary outcomes:
measure: all-cause death, recurrent MI, unplanned IRA-revascularization, stroke or definite stent thrombosis
timeFrame: 30 days
measure: major bleeding complications
timeFrame: 30 days
measure: cardiac death
timeFrame: 30 days
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Deutsches Herzzentrum Muenchen
state: Bavaria
city: Munich
country: Germany
facility: Klinikum rechts der Isar, Technische Universitaet Muenchen
state: Bavaria
city: Bad Segeberg
country: Germany
facility: Herzzentrum der Segeberger Kliniken
Study officials:
affiliation: Deutsches Herzzentrum Muenchen
name: Julinda Mehilli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Deutsches Herzzentrum Muenchen
name: Adnan Kastrati, MD
role: STUDY_CHAIR
References:
citation: Schulz S, Richardt G, Laugwitz KL, Morath T, Neudecker J, Hoppmann P, Mehran R, Gershlick AH, Tolg R, Anette Fiedler K, Abdel-Wahab M, Kufner S, Schneider S, Schunkert H, Ibrahim T, Mehilli J, Kastrati A; Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 Investigators. Prasugrel plus bivalirudin vs. clopidogrel plus heparin in patients with ST-segment elevation myocardial infarction. Eur Heart J. 2014 Sep 7;35(34):2285-94. doi: 10.1093/eurheartj/ehu182. Epub 2014 May 9.
citation: Schulz S, Richardt G, Laugwitz KL, Mehran R, Gershlick AH, Morath T, Mayer K, Neudecker J, Tolg R, Ibrahim T, Hauschke D, Braun D, Schunkert H, Kastrati A, Mehilli J; Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 Investigators. Comparison of prasugrel and bivalirudin vs clopidogrel and heparin in patients with ST-segment elevation myocardial infarction: Design and rationale of the Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 trial. Clin Cardiol. 2014 May;37(5):270-6. doi: 10.1002/clc.22268. Epub 2014 Mar 14.