Efficacy Study of Combined Prasugrel and Bivalirudin Versus Clopidogrel and Heparin in Myocardial Infarction

Study Overview
=================
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.

Official Title
-----------------
Randomized Trial of Prasugrel Plus Bivalirudin vs. Clopidogrel Plus Heparin in Patients With Acute STEMI

Conditions
-----------------
Myocardial Infarction

Intervention / Treatment
-----------------
* Drug: Prasugrel
* Drug: Bivalirudin
* Drug: Clopidogrel
* Drug: Heparin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients presenting within 24 hours from the onset of symptoms with STEMI Informed, written consent In women with childbearing potential a pregnancy test is obligatory. Exclusion Criteria: Age < 18 years Cardiogenic shock Active bleeding; bleeding diathesis; coagulopathy History of gastrointestinal or genitourinary bleeding <2 months Refusal to receive blood transfusion Major surgery in the last 6 weeks History of intracranial bleeding or structural abnormalities Suspected aortic dissection Heparin-induced thrombocytopenia Any previous stroke Prior administration of thrombolytics, bivalirudin, low-molecular weight heparin or fondaparinux for the index MI Known relevant hematological deviations: Hb <100g/l, Thromb. <100x10^9/l Use of coumadin derivatives within the last 7 days Chronic therapy with nonsteroidal anti-inflammatory drugs (except aspirin), COX-2 inhibitors, prasugrel Known malignancies or other comorbid conditions with life expectancy <1 year Known severe liver disease, severe renal failure Known allergy to the study medications Previous enrollment in this trial Pregnancy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prasugrel + Bivalirudin<br>60 mg prasugrel plus bivalirudin | Drug: Prasugrel<br>* 60 mg prasugrel as loading dose prior to PPCI<br>* Other names: Efient;Drug: Bivalirudin<br>* IV bolus 0.75 mg/kg of body weight followed by an infusion of 1.75 mg/kg/hour during the PPCI<br>* Other names: Angiox;|
| Active Comparator: Clopidogrel + Heparin<br>clopidogrel as loading and heparin | Drug: Clopidogrel<br>* 600 mg clopidogrel as loading dose before PPCI<br>* Other names: Plavix;Drug: Heparin<br>* i.v. bolus of 70-100 IU/kg body weight<br>* Other names: unfractionated Heparin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| composite of all-cause death, recurrent MI, unplanned IRA revascularization, stroke, definite stent thrombosis or major bleeding |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| all-cause death, recurrent MI, unplanned IRA-revascularization, stroke or definite stent thrombosis |  | 30 days | 
| major bleeding complications |  | 30 days | 
| cardiac death |  | 30 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
myocardial infarction, clopidogrel, prasugrel, bivalirudin, primary PCI