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

Phase 4

Completed

• Conditions: Coronary Disease; Angina, Unstable
• Interventions: Drug: Abciximab; Drug: Placebo

• Registration Number: NCT00133003
• Lead Sponsor: Deutsches Herzzentrum Muenchen

Brief Summary

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

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 Ticlopidine also reduces procedural complications but has a delayed onset of action after coronary stenting and has been replaced by clopidogrel, which provides similar efficacy and is associated with fewer side effects.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

Study Timeline

• Study Start: 2003-03
• Study First Submitted: 2005-08-18
• Study First Submitted QC: 2005-08-18
• Study First Posted: 2005-08-22
• Primary Completion: 2006-01
• Study Completion: 2006-01
• Status Verified: 2008-04
• Last Update Submitted: 2008-04-12
• Last Update Posted: 2008-04-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2022

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Abciximab	-
2	Placebo	-

Primary Outcome Measures

Name	Time	Method
Composite rate of death, myocardial infarction, and urgent target vessel revascularization within 30 days	30 days

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (5)

Deutsches Herzzentrum Muenchen; 🇩🇪 Munich, Germany

First Medizinische Klinik, Klinikum rechts der Isar; 🇩🇪 Munich, Germany

St. Antonius Ziekenhuis Hospital; 🇳🇱 Nieuwegein, Netherlands

Herz-Zentrum; 🇩🇪 Bad Krozingen, Germany

Instituto Dante Pazzanese de Cardiologia; 🇧🇷 São Paulo, Brazil