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

Condition(s) targeted: Myocardial Infarction; Coronary Disease

Intervention: Abciximab + UFH (Drug); Bivalirudin (Drug); Heparin (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Deutsches Herzzentrum Muenchen

Official(s) and/or principal investigator(s):
Albert Schoemig, MD, Study Chair, Affiliation: Deutsches Herzzentrum Muenchen
Adnan Kastrati, MD, Principal Investigator, Affiliation: Deutsches Herzzentrum Muenchen

Overall contact:
Julinda Mehilli, MD, Phone: +49 89 12184582, Email: mehilli@dhm.mhn.de

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.

Official title: Prospective, 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)

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Efficacy Study

Primary outcome: Composite of death, large recurrent myocardial infarction (MI), urgent target vessel revascularization (TVR) or major bleeding

Secondary outcome:

Composite end point of death, any recurrent myocardial infarction or urgent TVR

Major bleedings

Detailed 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.

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

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

Julinda Mehilli, MD, Phone: +49 89 12184582, Email: mehilli@dhm.mhn.de

Medizinische Klinik, Klinikum rechts der Isar, Muenchen 81675, Germany; Recruiting
Josef Dirschinger, MD, Phone: +49 89 4140 2947
Josef Dirschinger, MD, Principal Investigator

Deutsches Herzzentrum Muenchen, Munich 80636, Germany; Recruiting
Adnan Kastrati, MD, Phone: +49 89 1218 4577, Email: kastrati@dhm.mhn.de
Adnan Kastrati, MD, Principal Investigator

Herz-Zentrum Bad Krozingen, Bad Krozingen 79189, Germany; Recruiting
Jan Minners, MD, Phone: +49 7633 402, Ext: 2465, Email: jan.minners@herzzentrum.de
Jan Minners, MD, Principal Investigator

Herz- und Gefaessklinik, Kardiologie, Bad Neustadt 97616, Germany; Not yet recruiting
Gabriele Rosshirt, Phone: +49 9771 66, Ext: 2177, Email: g.rosshirt@kardiologie-bad-neustadt.de
Michael Schneider, MD, Principal Investigator

Marienhospital Osnabrueck, Osnabrueck 49074, Germany; Not yet recruiting
von Strohr, Phone: +49 541 326, Ext: 4662, Email: rwessely@mho.de
Rainer Wessely, MD, Principal Investigator

Vivantes Auguste Viktoria Klinikum, Berlin 12157, Germany; Recruiting
Goshtasb, MD, Phone: +49 30 13020, Ext: 8401
Schuehlen Helmut, MD, Principal Investigator

Vivantes Klinikum Neukoelln, Berlin 12351, Germany; Recruiting
Mrs. Marselli, Phone: +49-30-13014, Ext: 2359
Harald Darius, MD, Principal Investigator

Vivantes Klinikum im Friedrichshain, Berlin 10249, Germany; Not yet recruiting
Mrs. Rasenack, Phone: +49 30 13023, Ext: 1591
Mr. Hoffmann, MD, Principal Investigator

Ospedale Cageggi, Firenze 50134, Italy; Recruiting
Fabio Torrini, ?, Phone: +39 55 427, Ext: 7111, Email: carddept@tin.it
Guido Parodi, MD, Principal Investigator

Related publications:

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. No abstract available.

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

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.

Silber S, Albertsson P, Aviles FF, Camici PG, Colombo A, Hamm C, Jorgensen 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.

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. Epub 2006 Mar 13.

Starting date: July 2006
Ending date: August 2010
Last updated: September 6, 2009