Randomized Comparison of Abciximab Plus Heparin With Bivalirudin in Acute Coronary Syndrome

Myocardial Infarction Clinical Trial

— ISAR-REACT-4  

Official title:

Randomized, Double-Blind, Active-Controlled, Multicenter Trial of Abciximab And Bivalirudin in Patients With Non-ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Interventions (ISAR-REACT-4)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00373451
• Other study ID #: GE IDE No. A01106
• Status: Completed
• Phase: Phase 4
• First received: September 7, 2006
• Last updated: May 7, 2012
• Start date: July 2006
• Est. completion date: July 2011

Study information

• Verified date: May 2012
• 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 which of these anti-clotting medications, abciximab plus unfractionated heparin or bivalirudin, is more effective to prevent thrombotic and bleeding complications in patients suffering from a heart attack and undergoing coronary intervention.

Description:

Non-ST elevation myocardial infarction (NSTEMI) is associated with an increased risk of death and is a major reason for hospital admissions. Most frequently, the sequence of events that leads to NSTEMI is characterized by a disrupted atherosclerotic plaque, platelet activation and aggregation, thrombus formation and microembolizations. Patients with NSTEMI are treated with an early invasive strategy and there is intensive work in progress to define the optimal antithrombotic therapy to be used in adjunct to percutaneous coronary intervention (PCI) in these patients. Bivalirudin, a direct thrombin inhibitor, and the glycoprotein IIb/IIIa inhibitor (GPI) abciximab have been in the focus of recent trials in patients with acute coronary syndrome (ACS). In a recent randomized, open-label trial (ACUITY trial), patients with the suspicion of ACS on the basis of the type of anginal symptoms, ST-segment displacement, elevated biomarkers or several risk indicators were randomized to receive bivalirudin alone with bail-out GPIs, bivalirudin plus GPIs, or heparin/low-molecular weight heparin plus a GPI. The GPIs most frequently used were eptifibatide and tirofiban. Abciximab was given in only < 9% of the cases. In another randomized, double-blind, placebo-controlled trial (ISAR-REACT-2) including ACS patients undergoing PCI, abciximab was administered in cath lab and was associated with a significant reduction of ischemic events in patients with NSTEMI, and did not lead to a measurable increase in major bleeding complications. However, it is not known whether abciximab is also superior to bivalirudin in patients with NSTEMI. We designed this study to assess whether abciximab added to unfractionated heparin is superior to bivalirudin in patients with NSTEMI.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1721
• Est. completion date: July 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Episode of unstable angina

• Elevated cardiac markers

• Angiographic lesions requiring PCI

• Informed, written consent

Exclusion Criteria:

• Age < 18 years and > 80 years

• ST-segment elevation acute myocardial infarction within 48 hours

• Cardiogenic shock

• Pericarditis

• Malignancies or other comorbid conditions with life expectancy less than one year or that may result in protocol non-compliance

• Active bleeding; bleeding diathesis; history of gastrointestinal or genitourinary bleeding, recent trauma or major surgery in the last month; history of intracranial bleeding or structural abnormalities; suspected aortic dissection; pericarditis; and patient's refusal to blood transfusion

• Oral anticoagulation therapy with coumarin derivative within the last 7 days

• Recent use of GPIIb/IIIa inhibitors within 14 days

• Treatment with unfractionated heparin within 4 hours unless ACT > 150sec; or low-molecular weight heparin within 8 hours before randomization

• Treatment with bivalirudin within 24 hours before randomization

• Severe uncontrolled hypertension > 180/110 mm Hg unresponsive to therapy

• Planned staged PCI procedure within 30 days from index procedure or prior PCI within the last 30 days

• Relevant hematologic deviations

• Glomerular filtration rate (GFR) < 30 ml/min or serum creatinine > 30 mg/L or dependence on renal dialysis

• Known allergy or intolerance to the study medications, stainless steel or true anaphylaxis after prior exposure to contrast media

• Previous enrollment in this trial

• Women who are known to be pregnant, who are of childbearing potential and test positive for pregnancy, who have given birth within the last 90 days, who are breastfeeding

• Patient's inability to fully cooperate with the study protocol

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

• Coronary Artery Disease
• Coronary Disease
• Infarction
• Myocardial Infarction

Intervention

Drug:
• Abciximab + UFH
Abciximab (0.25 mg/kg of body weight bolus, followed by a 0.125 µg/kg/minute [maximum of 10 µg/minute] infusion for 12 hours)
• Bivalirudin
Bivalirudin (intravenous bolus of 0.75 mg/kg prior to the start of the intervention, followed by infusion of 1.75 mg/kg per hour for the duration of the procedure)
• Heparin
i.v. bolus of 70 units/kg/body weight of unfractionated heparin

Locations

Country	Name	City	State
Germany	Herz-Zentrum Bad Krozingen	Bad Krozingen
Germany	Herz- und Gefaessklinik, Kardiologie	Bad Neustadt
Germany	Vivantes Auguste Viktoria Klinikum	Berlin
Germany	Vivantes Klinikum im Friedrichshain	Berlin
Germany	Vivantes Klinikum Neukoelln	Berlin
Germany	Medizinische Klinik, Klinikum rechts der Isar	Muenchen
Germany	Deutsches Herzzentrum Muenchen	Munich
Germany	Marienhospital Osnabrueck	Osnabrueck
Italy	Ospedale Cageggi	Firenze

Sponsors (1)

Lead Sponsor	Collaborator
Deutsches Herzzentrum Muenchen

Countries where clinical trial is conducted

Germany,  Italy, 

References & Publications (5)

Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, Jones RH, Kereiakes D, Kupersmith J, Levin TN, Pepine CJ, Schaeffer JW, Smith EE 3rd, Steward DE, Theroux P, Gibbons RJ, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Smith SC Jr; American College of Cardiology; American Heart Association. Committee on the Management of Patients With Unstable Angina. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction--summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol. 2002 Oct 2;40(7):1366-74. — View Citation

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 (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. Epub 2006 Mar 13. — 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

Schulman SP. Antiplatelet therapy in non-ST-segment elevation acute coronary syndromes. JAMA. 2004 Oct 20;292(15):1875-82. — View Citation

Silber S, Albertsson P, Avilés FF, Camici PG, Colombo A, Hamm C, Jørgensen E, Marco J, Nordrehaug JE, Ruzyllo W, Urban P, Stone GW, Wijns W; Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Eur Heart J. 2005 Apr;26(8):804-47. Epub 2005 Mar 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of death, large recurrent myocardial infarction (MI), urgent target vessel revascularization (TVR) or major bleeding		30 days	Yes
Secondary	Composite end point of death, any recurrent myocardial infarction or urgent TVR		30 days	No
Secondary	Major bleedings		30 days	Yes