Un-fractionated Heparin Versus Bivalirudin During Percutaneous Coronary Interventions (PCI) (ISAR-REACT-3)

Sponsor

Deutsches Herzzentrum Muenchen (Other)

Overall Status

Completed

CT.gov ID

NCT00262054

Collaborator

(none)

4,570

Enrollment

Locations

Arms

Duration (Months)

1142.5

Patients Per Site

38.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether bivalirudin given during PCI is associated with better outcomes compared to un-fractionated heparin.

Condition or Disease	Intervention/Treatment	Phase
Coronary Disease Angina Pectoris	Drug: Bivalirudin Drug: Un-fractionated heparin	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

4570 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, 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

Study Start Date :

Nov 1, 2005

Actual Primary Completion Date :

Feb 1, 2008

Actual Study Completion Date :

May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A 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.	Drug: Bivalirudin 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 Names: 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.

Arm

Intervention/Treatment

Experimental: A

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.

Drug: Bivalirudin

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 Names:

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.

Outcome Measures

Primary Outcome Measures

Composite rate of death, myocardial infarction (MI),urgent target vessel revascularization (TVR) within 30 days or in-hospital major bleeding [30 days]

Secondary Outcome Measures

Composite rate of death, MI or urgent TVR within 30 days [30 days]
Composite rate of death, MI or TVR at 1 year [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients older than 18 years of age to undergo PCI
Clopidogrel loading at least 2 hrs prior to PCI according to the PCI guidelines
Informed, written consent

Exclusion Criteria:

Recent ST-elevation myocardial infarction within the last 48 hours
Cardiogenic shock
ACS and positive biomarkers (Troponin T > 0.03 µg/L)
Malignancies or other comorbid conditions (for example severe liver, renal and pancreatic disease) with life expectancy less than one year or that may result in protocol non-compliance
Active bleeding; bleeding diathesis
History of gastrointestinal or genitourinary bleeding within the last 6 weeks
Presence of diseases which have a high probability of vascular lesions and subsequent bleeding such as active gastric ulcer or active ulcerous colitis
Recent trauma or major surgery in the last month
Ophthalmic surgery or brain surgery in the last month
Retinopathies or vitreous body bleeding in the last month
History of intracranial bleeding or structural abnormalities (for example aneurysm of cerebral arteries)
Suspected aortic dissection; pericarditis and subacute bacterial endocarditis
Patient's refusal to blood transfusion
Oral anticoagulation therapy with coumarin derivative within the last 7 days
Treatment with UFH within 6 hours or low-molecular weight heparin within 8 hours before randomization
Treatment with bivalirudin within 24 hours before randomization
Severe uncontrolled hypertension >180/110 mmHg unresponsive to therapy
Planned staged PCI procedure within 30 days from index procedure or prior PCI within the last 30 days
Relevant hematologic deviations:hemoglobin < 100 g/L; platelet count < 100 x 109 /L
Glomerular filtration rate (GFR) < 30 ml/min or serum creatinine > 30 mg/L or dependence on renal dialysis
Known allergy to the study medications: aspirin, clopidogrel, UFH, bivalirudin; stainless steel; true anaphylaxis after prior exposure to contrast media
Known heparin-induced thrombocytopenia (Typ II)
Previous enrollment in this trial
Pregnancy (present, suspected or planned) or positive pregnancy test
Spinal, peridural and epidural anesthesia
Patient's inability to fully cooperate with the study protocol

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Herz-Zentrum	Bad Krozingen	Germany	79189
2	Segeberger Kliniken	Bad Segeberg	Germany	23795
3	Deutsches Herzzentrum Muenchen	Munich	Germany	80636
4	First Medizinische Klinik, Klinikum rechts der Isar	Munich	Germany	81675