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

Coronary Disease Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00133003
• Other study ID #: GE IDE No. A00500
• Status: Completed
• Phase: Phase 4
• First received: August 18, 2005
• Last updated: April 12, 2008
• Start date: March 2003
• Est. completion date: January 2006

Study information

• Verified date: April 2008
• Source: Deutsches Herzzentrum Muenchen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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 Ticlopidine also reduces procedural complications but has a delayed onset of action after coronary stenting and has been replaced by clopidogrel, which provides similar efficacy and is associated with fewer side effects.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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2022
• Est. completion date: January 2006
• Est. primary completion date: January 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Angina, Unstable
• Coronary Artery Disease
• Coronary Disease

Intervention

Drug:
• Abciximab
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
• Placebo
Placebo consist of placebo bolus and infusion of 12 hours (NaCl 0.9%), plus heparin bolus, 140 U/kg of body weight

Locations

Country	Name	City	State
Brazil	Instituto Dante Pazzanese de Cardiologia	São Paulo
Germany	Herz-Zentrum	Bad Krozingen
Germany	Deutsches Herzzentrum Muenchen	Munich
Germany	First Medizinische Klinik, Klinikum rechts der Isar	Munich
Netherlands	St. Antonius Ziekenhuis Hospital	Nieuwegein

Sponsors (2)

Lead Sponsor	Collaborator
Deutsches Herzzentrum Muenchen	Technische Universität München

Countries where clinical trial is conducted

Brazil,  Germany,  Netherlands, 

References & Publications (7)

Kastrati A, Mehilli J, Neumann FJ, Dotzer F, ten Berg J, Bollwein H, Graf I, Ibrahim M, Pache J, Seyfarth M, Schühlen H, Dirschinger J, Berger PB, Schömig A; Intracoronary Stenting and Antithrombotic: Regimen Rapid Early Action for Coronary Treatment 2 (I — View Citation

Kastrati A, Mehilli J, Schühlen H, Dirschinger J, Dotzer F, ten Berg JM, Neumann FJ, Bollwein H, Volmer C, Gawaz M, Berger PB, Schömig A; Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action for Coronary Treatment Study Investigators. A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel. N Engl J Med. 2004 Jan 15;350(3):232-8. — View Citation

Müller I, Seyfarth M, Rüdiger S, Wolf B, Pogatsa-Murray G, Schömig A, Gawaz M. Effect of a high loading dose of clopidogrel on platelet function in patients undergoing coronary stent placement. Heart. 2001 Jan;85(1):92-3. — View Citation

Neumann FJ, Kastrati A, Pogatsa-Murray G, Mehilli J, Bollwein H, Bestehorn HP, Schmitt C, Seyfarth M, Dirschinger J, Schömig A. Evaluation of prolonged antithrombotic pretreatment ("cooling-off" strategy) before intervention in patients with unstable coronary syndromes: a randomized controlled trial. JAMA. 2003 Sep 24;290(12):1593-9. — View Citation

Pache J, Kastrati A, Mehilli J, Gawaz M, Neumann FJ, Seyfarth M, Hall D, Braun S, Dirschinger J, Schömig A. Clopidogrel therapy in patients undergoing coronary stenting: value of a high-loading-dose regimen. Catheter Cardiovasc Interv. 2002 Apr;55(4):436-41. — View Citation

Topol EJ, Mark DB, Lincoff AM, Cohen E, Burton J, Kleiman N, Talley D, Sapp S, Booth J, Cabot CF, Anderson KM, Califf RM. Outcomes at 1 year and economic implications of platelet glycoprotein IIb/IIIa blockade in patients undergoing coronary stenting: results from a multicentre randomised trial. EPISTENT Investigators. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting. Lancet. 1999 Dec 11;354(9195):2019-24. Erratum in: Lancet 2000 Mar 25;355(9209):1104. — View Citation

Topol EJ, Moliterno DJ, Herrmann HC, Powers ER, Grines CL, Cohen DJ, Cohen EA, Bertrand M, Neumann FJ, Stone GW, DiBattiste PM, Demopoulos L; TARGET Investigators. Do Tirofiban and ReoPro Give Similar Efficacy Trial. Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization. N Engl J Med. 2001 Jun 21;344(25):1888-94. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite rate of death, myocardial infarction, and urgent target vessel revascularization within 30 days		30 days	No
Secondary	Major and minor bleeding complications in-hospital		in hospital	Yes
Secondary	Death or myocardial infarction by 12 months		12 months	No
Secondary	Target vessel revascularization by 12 months		12 months	No