ISAR-REACT-4: Randomized Comparison of Abciximab Plus Heparin With Bivalirudin in Acute Coronary Syndrome

Sponsor

Deutsches Herzzentrum Muenchen (Other)

Overall Status

Completed

CT.gov ID

NCT00373451

Collaborator

(none)

1,721

Enrollment

Locations

Arms

Duration (Months)

191.2

Patients Per Site

3.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine which of these anti-clotting medications, abciximab plus unfractionated heparin or bivalirudin, is more effective to prevent thrombotic and bleeding complications in patients suffering from a heart attack and undergoing coronary intervention.

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction Coronary Disease	Drug: Abciximab + UFH Drug: Bivalirudin Drug: Heparin	Phase 4

Detailed Description

Non-ST elevation myocardial infarction (NSTEMI) is associated with an increased risk of death and is a major reason for hospital admissions. Most frequently, the sequence of events that leads to NSTEMI is characterized by a disrupted atherosclerotic plaque, platelet activation and aggregation, thrombus formation and microembolizations. Patients with NSTEMI are treated with an early invasive strategy and there is intensive work in progress to define the optimal antithrombotic therapy to be used in adjunct to percutaneous coronary intervention (PCI) in these patients. Bivalirudin, a direct thrombin inhibitor, and the glycoprotein IIb/IIIa inhibitor (GPI) abciximab have been in the focus of recent trials in patients with acute coronary syndrome (ACS). In a recent randomized, open-label trial (ACUITY trial), patients with the suspicion of ACS on the basis of the type of anginal symptoms, ST-segment displacement, elevated biomarkers or several risk indicators were randomized to receive bivalirudin alone with bail-out GPIs, bivalirudin plus GPIs, or heparin/low-molecular weight heparin plus a GPI. The GPIs most frequently used were eptifibatide and tirofiban. Abciximab was given in only < 9% of the cases. In another randomized, double-blind, placebo-controlled trial (ISAR-REACT-2) including ACS patients undergoing PCI, abciximab was administered in cath lab and was associated with a significant reduction of ischemic events in patients with NSTEMI, and did not lead to a measurable increase in major bleeding complications. However, it is not known whether abciximab is also superior to bivalirudin in patients with NSTEMI. We designed this study to assess whether abciximab added to unfractionated heparin is superior to bivalirudin in patients with NSTEMI.

Study Design

Study Type:

Interventional

Actual Enrollment :

1721 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Randomized, Double-Blind, Active-Controlled, Multicenter Trial of Abciximab And Bivalirudin in Patients With Non-ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Interventions (ISAR-REACT-4)

Study Start Date :

Jul 1, 2006

Actual Primary Completion Date :

May 1, 2011

Actual Study Completion Date :

Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Abciximab+UFH Abciximab and unfractionated heparin as bolus given during PCI and abciximab-perfusion for 12 hours after PCI	Drug: Abciximab + UFH Abciximab (0.25 mg/kg of body weight bolus, followed by a 0.125 µg/kg/minute [maximum of 10 µg/minute] infusion for 12 hours) Other Names: ReoPro Drug: Heparin i.v. bolus of 70 units/kg/body weight of unfractionated heparin Other Names: unfractionated heparin
Active Comparator: Bivalirudin Bivalirudin given only during PCI	Drug: Bivalirudin Bivalirudin (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: Angiox

Arm

Intervention/Treatment

Experimental: Abciximab+UFH

Abciximab and unfractionated heparin as bolus given during PCI and abciximab-perfusion for 12 hours after PCI

Drug: Abciximab + UFH

Abciximab (0.25 mg/kg of body weight bolus, followed by a 0.125 µg/kg/minute [maximum of 10 µg/minute] infusion for 12 hours)

Other Names:

ReoPro

Drug: Heparin

i.v. bolus of 70 units/kg/body weight of unfractionated heparin

Other Names:

unfractionated heparin

Active Comparator: Bivalirudin

Bivalirudin given only during PCI

Drug: Bivalirudin

Bivalirudin (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:

Angiox

Outcome Measures

Primary Outcome Measures

Composite of death, large recurrent myocardial infarction (MI), urgent target vessel revascularization (TVR) or major bleeding [30 days]

Secondary Outcome Measures

Composite end point of death, any recurrent myocardial infarction or urgent TVR [30 days]
Major bleedings [30 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Episode of unstable angina
Elevated cardiac markers
Angiographic lesions requiring PCI
Informed, written consent

Exclusion Criteria:

Age < 18 years and > 80 years
ST-segment elevation acute myocardial infarction within 48 hours
Cardiogenic shock
Pericarditis
Malignancies or other comorbid conditions 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, recent trauma or major surgery in the last month; history of intracranial bleeding or structural abnormalities; suspected aortic dissection; pericarditis; and patient's refusal to blood transfusion
Oral anticoagulation therapy with coumarin derivative within the last 7 days
Recent use of GPIIb/IIIa inhibitors within 14 days
Treatment with unfractionated heparin within 4 hours unless ACT > 150sec; or low-molecular weight heparin within 8 hours before randomization
Treatment with bivalirudin within 24 hours before randomization
Severe uncontrolled hypertension > 180/110 mm Hg unresponsive to therapy
Planned staged PCI procedure within 30 days from index procedure or prior PCI within the last 30 days
Relevant hematologic deviations
Glomerular filtration rate (GFR) < 30 ml/min or serum creatinine > 30 mg/L or dependence on renal dialysis
Known allergy or intolerance to the study medications, stainless steel or true anaphylaxis after prior exposure to contrast media
Previous enrollment in this trial
Women who are known to be pregnant, who are of childbearing potential and test positive for pregnancy, who have given birth within the last 90 days, who are breastfeeding
Patient's inability to fully cooperate with the study protocol

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Herz-Zentrum Bad Krozingen	Bad Krozingen	Germany	79189
2	Herz- und Gefaessklinik, Kardiologie	Bad Neustadt	Germany	97616
3	Vivantes Klinikum im Friedrichshain	Berlin	Germany	10249
4	Vivantes Auguste Viktoria Klinikum	Berlin	Germany	12157
5	Vivantes Klinikum Neukoelln	Berlin	Germany	12351
6	Medizinische Klinik, Klinikum rechts der Isar	Muenchen	Germany	81675
7	Deutsches Herzzentrum Muenchen	Munich	Germany	80636
8	Marienhospital Osnabrueck	Osnabrueck	Germany	49074
9	Ospedale Cageggi	Firenze	Italy	50134