Clinical trial NCT00133003: Abciximab, Clopidogrel and Percutaneous Coronary Intervention in Acute Coronary Syndrome (ISAR-REACT-2)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Disease
Angina, Unstable
Lead sponsor: Deutsches Herzzentrum Muenchen
Sponsor class: OTHER
Collaborators: name: Technical University of Munich
First posted: 2005-08-22
Enrollment: 2022
Sex: ALL
Minimum age (years): 18
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 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 Ticlopidine also reduces procedural complications but has a delayed onset of action after coronary stenting and has been replaced by clopidogrel, which provides similar efficacy and is associated with fewer side effects.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.

Eligibility criteria: 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)

Primary outcomes:
measure: Composite rate of death, myocardial infarction, and urgent target vessel revascularization within 30 days
timeFrame: 30 days
Secondary outcomes:
measure: Major and minor bleeding complications in-hospital
timeFrame: in hospital
measure: Death or myocardial infarction by 12 months
timeFrame: 12 months
measure: Target vessel revascularization by 12 months
timeFrame: 12 months
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Instituto Dante Pazzanese de Cardiologia
city: Bad Krozingen
country: Germany
facility: Herz-Zentrum
city: Munich
country: Germany
facility: Deutsches Herzzentrum Muenchen
city: Munich
country: Germany
facility: First Medizinische Klinik, Klinikum rechts der Isar
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis Hospital
Study officials:
affiliation: Deutsches Herzzentrum Muenchen
name: Albert Schomig, MD
role: STUDY_CHAIR
affiliation: Deutsches Herzzentrum Muenchen
name: Adnan Kastrati, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke Clinical Research Institute
name: Peter B Berger, MD
role: STUDY_DIRECTOR
References:
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citation: Pache J, Kastrati A, Mehilli J, Gawaz M, Neumann FJ, Seyfarth M, Hall D, Braun S, Dirschinger J, Schomig A. Clopidogrel therapy in patients undergoing coronary stenting: value of a high-loading-dose regimen. Catheter Cardiovasc Interv. 2002 Apr;55(4):436-41. doi: 10.1002/ccd.10092.
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citation: Kastrati A, Mehilli J, Neumann FJ, Dotzer F, ten Berg J, Bollwein H, Graf I, Ibrahim M, Pache J, Seyfarth M, Schuhlen H, Dirschinger J, Berger PB, Schomig A; Intracoronary Stenting and Antithrombotic: Regimen Rapid Early Action for Coronary Treatment 2 (ISAR-REACT 2) Trial Investigators. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial. JAMA. 2006 Apr 5;295(13):1531-8. doi: 10.1001/jama.295.13.joc60034. Epub 2006 Mar 13.
citation: Ndrepepa G, Kastrati A, Mehilli J, Neumann FJ, ten Berg J, Bruskina O, Dotzer F, Seyfarth M, Pache J, Dirschinger J, Ulm K, Berger PB, Schomig A. Age-dependent effect of abciximab in patients with acute coronary syndromes treated with percutaneous coronary interventions. Circulation. 2006 Nov 7;114(19):2040-6. doi: 10.1161/CIRCULATIONAHA.106.642306. Epub 2006 Oct 23.