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

NCT ID: NCT00133003

Last Updated: 2008-04-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 2022 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-03-31
• Study Completion Date: 2006-01-31

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 Ticlopidine also reduces procedural complications but has a delayed onset of action after coronary stenting and has been replaced by clopidogrel, which provides similar efficacy and is associated with fewer side effects.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

Conditions

Coronary Disease; Angina, Unstable

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Group Type: ACTIVE_COMPARATOR

Abciximab

Intervention Type: DRUG

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

2

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

ReoPro

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Technical University of Munich

OTHER

Sponsor Role: collaborator

Deutsches Herzzentrum Muenchen

OTHER

Sponsor Role: lead

Responsible Party

Deutsches Herzzentrum Muenchen

Principal Investigators

Albert Schomig, MD

Role: STUDY_CHAIR

Deutsches Herzzentrum Muenchen

Adnan Kastrati, MD

Role: PRINCIPAL_INVESTIGATOR

Deutsches Herzzentrum Muenchen

Peter B Berger, MD

Role: STUDY_DIRECTOR

Duke Clinical Research Institute

Locations

Instituto Dante Pazzanese de Cardiologia

São Paulo, , Brazil

Herz-Zentrum

Bad Krozingen, , Germany

Deutsches Herzzentrum Muenchen

Munich, , Germany

First Medizinische Klinik, Klinikum rechts der Isar

Munich, , Germany

St. Antonius Ziekenhuis Hospital

Nieuwegein, , Netherlands

Countries

Brazil; Germany; Netherlands

References

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. doi: 10.1016/s0140-6736(99)10018-7.

Reference Type: BACKGROUND

PMID: 10636365 (View on PubMed)

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. doi: 10.1056/NEJM200106213442502.

Reference Type: BACKGROUND

PMID: 11419425 (View on PubMed)

Neumann FJ, Kastrati A, Pogatsa-Murray G, Mehilli J, Bollwein H, Bestehorn HP, Schmitt C, Seyfarth M, Dirschinger J, Schomig 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. doi: 10.1001/jama.290.12.1593.

Reference Type: BACKGROUND

PMID: 14506118 (View on PubMed)

Muller I, Seyfarth M, Rudiger S, Wolf B, Pogatsa-Murray G, Schomig 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. doi: 10.1136/heart.85.1.92. No abstract available.

Reference Type: BACKGROUND

PMID: 11119474 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11948888 (View on PubMed)

Kastrati A, Mehilli J, Schuhlen H, Dirschinger J, Dotzer F, ten Berg JM, Neumann FJ, Bollwein H, Volmer C, Gawaz M, Berger PB, Schomig 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. doi: 10.1056/NEJMoa031859.

Reference Type: BACKGROUND

PMID: 14724302 (View on PubMed)

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.

Reference Type: RESULT

PMID: 16533938 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 17060377 (View on PubMed)

Other Identifiers

GE IDE No. A00500

Identifier Type: -

Identifier Source: org_study_id