Abciximab, Clopidogrel and Percutaneous Coronary Intervention in Acute Coronary Syndrome (ISAR-REACT-2)

Study Overview
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Brief Summary
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The purpose of this study is to determine whether there is any additional benefit from abciximab administration during percutaneous coronary intervention in patients presenting with acute coronary syndromes after pre-treatment with 600mg of clopidogrel.

Detailed Description
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Although percutaneous coronary interventions (PCIs) are an established therapeutic approach in patients presenting with acute coronary syndrome (ACS), it is still unclear which the best antithrombotic therapy to be applied periprocedurally is. The EPISTENT trial has shown that adding abciximab (a glycoprotein [GP] IIb/IIIa receptor inhibitor) to the therapy with ticlopidine plus aspirin significantly reduces the incidence of ischemic complications (death, myocardial infarction or reinterventions) after coronary stent implantation. Ticlopidine also reduces procedural complications but has a delayed onset of action after coronary stenting and has been replaced by clopidogrel, which provides similar efficacy and is associated with fewer side effects. Experimental studies have shown that a 600 mg loading dose of clopidogrel is safe and acts rapidly leading to a maximal inhibition of platelet aggregation within 2 hours after administration. In the ISAR-REACT trial, a 600 mg loading dose of clopidogrel was well tolerated, and associated with such a low frequency of early complications that the use of abciximab offered no clinically measurable benefit at 30 days. Although patients with ACS have frequently been treated with a cooling-off strategy for >48 hours before undergoing PCI, the ISAR-COOL trial demonstrated that patients undergoing PCI within 6-12 hours of presentation with an ACS actually suffer a lower rate of ischemic complications than those for whom an invasive approach is delayed. However, patients with ACS represent a higher risk subset and may need a more potent antithrombotic regimen periprocedurally. Therefore, the results of ISAR REACT, which was performed in low and intermediate risk patients, should not be generalized to high risk patients. Comparison: All patients with non-ST-segment elevation acute coronary syndromes who will undergo coronary angiography willing to participate in the trial will receive a loading dose of 600 mg clopidogrel at least 2 hours prior to the procedure. Eligible patients who do not meet the exclusion criteria in whom angiography reveals that PCI is planned will be randomized to receive either abciximab plus low-dose heparin, 70 units/kg, or high dose heparin (140 units/kg) plus placebo.

Official Title
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Prospective, Randomized, Double-Blind, Placebo-Controlled Trial of the Glycoprotein IIb/IIIa Inhibition With Abciximab in Patients With ACS Undergoing Coronary Stenting After Pretreatment With a High Loading Dose of Clopidogrel (ISAR-REACT-2)

Conditions
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Coronary Disease, Angina, Unstable

Intervention / Treatment
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* Drug: Abciximab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with acute coronary syndromes Pretreatment (2 hours) with high loading dose (600 mg) clopidogrel Significant angiographic lesions amenable to and requiring a PCI Written informed consent Exclusion Criteria: ST-segment elevation acute myocardial infarction within 48 hours from symptom onset Hemodynamic instability Pericarditis Malignancies with life expectancy less than one year Increased risk of bleeding Oral anticoagulation therapy with coumarin derivative within 7 days Recent use of GPIIb/IIIa inhibitors within 14 days Severe uncontrolled hypertension >180 mmHg unresponsive to therapy Relevant hematologic deviations: hemoglobin < 100g/L or hematocrit < 34%; platelet count < 100 x 10^9/L or platelet count > 600 x 10^9/L. Known allergy to the study medication Pregnancy (present or suspected)

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Active Comparator: 1<br> | Drug: Abciximab<br>* 0.25 mg/kg of body weight bolus, followed by a 0.125-microg/kg per minute [maximum, 10 microg/min] infusion for 12 hours, plus heparin, 70 U/kg of body weight<br>* Other names: ReoPro;|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* Placebo consist of placebo bolus and infusion of 12 hours (NaCl 0.9%), plus heparin bolus, 140 U/kg of body weight<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite rate of death, myocardial infarction, and urgent target vessel revascularization within 30 days |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major and minor bleeding complications in-hospital |  | in hospital | 
| Death or myocardial infarction by 12 months |  | 12 months | 
| Target vessel revascularization by 12 months |  | 12 months |