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

German Heart Center Munich

Status and phase

Completed

Phase 4

Conditions

Angina, Unstable

Coronary Disease

Treatments

Drug: Abciximab

Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT00133003

GE IDE No. A00500

Details and patient eligibility

About

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.

Full description

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 Ticlopidine also reduces procedural complications but has a delayed onset of action after coronary stenting and has been replaced by clopidogrel, which provides similar efficacy and is associated with fewer side effects.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.

Enrollment

2,022 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)