Randomized Comparison of Abciximab Plus Heparin With Bivalirudin in Acute Coronary Syndrome

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Myocardial Infarction, Coronary Disease

Intervention / Treatment
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* Drug: Abciximab + UFH
* Drug: Bivalirudin
* Drug: Heparin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abciximab+UFH<br>Abciximab and unfractionated heparin as bolus given during PCI and abciximab-perfusion for 12 hours after PCI | Drug: Abciximab + UFH<br>* 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)<br>* Other names: ReoPro;Drug: Heparin<br>* i.v. bolus of 70 units/kg/body weight of unfractionated heparin<br>* Other names: unfractionated heparin;|
| Active Comparator: Bivalirudin<br>Bivalirudin given only during PCI | Drug: Bivalirudin<br>* 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)<br>* Other names: Angiox;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of death, large recurrent myocardial infarction (MI), urgent target vessel revascularization (TVR) or major bleeding |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite end point of death, any recurrent myocardial infarction or urgent TVR |  | 30 days | 
| Major bleedings |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSTEMI