Clinical trial NCT00373451: Randomized Comparison of Abciximab Plus Heparin With Bivalirudin in Acute Coronary Syndrome
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Myocardial Infarction
Coronary Disease
Keywords: NSTEMI
Lead sponsor: Deutsches Herzzentrum Muenchen
Sponsor class: OTHER
First posted: 2006-09-08
Enrollment: 1721
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Composite of death, large recurrent myocardial infarction (MI), urgent target vessel revascularization (TVR) or major bleeding
timeFrame: 30 days
Secondary outcomes:
measure: Composite end point of death, any recurrent myocardial infarction or urgent TVR
timeFrame: 30 days
measure: Major bleedings
timeFrame: 30 days
Other outcomes:
Locations:
city: Bad Krozingen
country: Germany
facility: Herz-Zentrum Bad Krozingen
city: Bad Neustadt
country: Germany
facility: Herz- und Gefaessklinik, Kardiologie
city: Berlin
country: Germany
facility: Vivantes Klinikum im Friedrichshain
city: Berlin
country: Germany
facility: Vivantes Auguste Viktoria Klinikum
city: Berlin
country: Germany
facility: Vivantes Klinikum Neukoelln
city: Muenchen
country: Germany
facility: Medizinische Klinik, Klinikum rechts der Isar
city: Munich
country: Germany
facility: Deutsches Herzzentrum Muenchen
city: Osnabrueck
country: Germany
facility: Marienhospital Osnabrueck
city: Firenze
country: Italy
facility: Ospedale Cageggi
Study officials:
affiliation: Deutsches Herzzentrum Muenchen
name: Albert Schoemig, MD
role: STUDY_CHAIR
affiliation: Deutsches Herzzentrum Muenchen
name: Adnan Kastrati, MD
role: PRINCIPAL_INVESTIGATOR
References:
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