Un-fractionated Heparin Versus Bivalirudin During Percutaneous Coronary Interventions (PCI) (ISAR-REACT-3)
The purpose of this study is to determine whether bivalirudin given during PCI is associated with better outcomes compared to un-fractionated heparin.
Drug: Un-fractionated heparin
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Prospective, Randomized, Double-Blind, Active-Controlled, Multicenter Trial of Bivalirudin and Un-fractionated Heparin in Patients Undergoing Percutaneous Coronary Interventions. ISAR-REACT-3|
- Composite rate of death, myocardial infarction (MI),urgent target vessel revascularization (TVR) within 30 days or in-hospital major bleeding [ Time Frame: 30 days ] [ Designated as safety issue: No ]
- Composite rate of death, MI or urgent TVR within 30 days [ Time Frame: 30 days ] [ Designated as safety issue: No ]
- Composite rate of death, MI or TVR at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
|Study Start Date:||November 2005|
|Study Completion Date:||May 2008|
|Primary Completion Date:||February 2008 (Final data collection date for primary outcome measure)|
bivalirudin is to be administered as an intravenous bolus of 0.75 mg/kg prior to the start of the intervention, followed by infusion of 1.75 mg/kg per hour for the duration of the procedure.
bivalirudin to be administered as an intravenous bolus of 0.75 mg/kg prior to the start of the intervention, followed by infusion of 1.75 mg/kg per hour for the duration of the procedure.
Other Name: ReoPro
Active Comparator: B
UFH given as an intravenous bolus of 140 units/kg. Double blinding will be maintained by using a double-dummy technique consisting of identical UFH and bivalirudin syringes and bivalirudin or placebo infusion bags.
Drug: Un-fractionated heparin
UFH is given as an intravenous bolus of 140 units/kg followed by infusion of placebo 1.75 mg/kg per hour for the duration of the procedure.
Thrombin plays a major role in acute coronary artery occlusions during percutaneous coronary interventions. Unfractionated heparin has been traditionally used during invasive coronary procedures to reduce the risk of thrombotic occlusion. Bivalirudin, a direct antithrombin inhibitor, has several advantages over unfractionated heparin: it acts independently of antithrombin and inhibits both free and clot-bound thrombin; it is not neutralized by circulating inhibitors; exhibits consistent dose-response characteristics, and does not cause thrombocytopenia. Previous studies have shown that use of bivalirudin among patients undergoing percutaneous coronary interventions is associated with better outcomes (death, myocardial infarction, urgent repeat revascularization or in-hospital major bleeding) as compared with unfractionated heparin and adjunctive use of glycoprotein IIb/IIIa platelet receptor inhibitors. However, previous studies have included patients treated with plain balloon angioplasty or stenting after inadequate pre-treatment with thienopyridines (ticlopidine or clopidogrel). Recent guidelines recommend that all patients undergoing percutaneous coronary interventions must receive a loading dose of 300 -600 mg of clopidogrel. A 600 mg loading dose of clopidogrel eliminates the need for glycoprotein IIb/IIIa platelet receptor inhibitors in adjunct to heparin. According to existing evidence antithrombotic regimens based on either bivalirudin or pre-treatment with 600 mg of clopidogrel in addition to UFH intraprocedurally, are effective strategies to reduce ischemic and hemorrhagic complications in patients with coronary artery disease undergoing PCI. At present, it is not known whether bivalirudin is superior to UHF in patients who have been optimally pre-treated with a loading dose of clopidogrel.
|Bad Krozingen, Germany, 79189|
|Bad Segeberg, Germany, 23795|
|Deutsches Herzzentrum Muenchen|
|Munich, Germany, 80636|
|First Medizinische Klinik, Klinikum rechts der Isar|
|Munich, Germany, 81675|
|Study Chair:||Albert Schomig, MD||Deutsches Herzzentrum Muenchen|
|Principal Investigator:||Adnan Kastrati, MD||Deutsches Herzzentrum Muenchen|
|Study Director:||Franz-Josef Neumann, MD||Herz-Zentrum Bad Krozingen|