Un-Fractionated Heparin Versus Bivalirudin During Percutaneous Coronary Interventions (PCI) (ISAR-REACT-3) - Full Text View

Sponsored by:	Deutsches Herzzentrum Muenchen
Information provided by:	Deutsches Herzzentrum Muenchen
ClinicalTrials.gov Identifier:	NCT00262054

Purpose

The purpose of this study is to determine whether bivalirudin given during PCI is associated with better outcomes compared to un-fractionated heparin.

Condition	Intervention	Phase
Coronary Disease Angina Pectoris	Drug: Bivalirudin Drug: Un-fractionated heparin	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Efficacy Study
Official Title:	Prospective, Randomized, Double-Blind, Active-Controlled, Multicenter Trial of Bivalirudin and Un-Fractionated Heparin in Patients Undergoing Percutaneous Coronary Interventions. ISAR-REACT-3

Resource links provided by NLM:

MedlinePlus related topics: Angina Blood Thinners Coronary Artery Disease

Drug Information available for: Bivalirudin Heparin

U.S. FDA Resources

Further study details as provided by Deutsches Herzzentrum Muenchen:

Primary Outcome Measures:

Composite rate of death, myocardial infarction (MI),urgent target vessel revascularization (TVR) within 30 days or in-hospital major bleeding [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Composite rate of death, MI or urgent TVR within 30 days [ Time Frame: 30 days ] [ Designated as safety issue: No ]
Composite rate of death, MI or TVR at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment:	4570
Study Start Date:	November 2005
Study Completion Date:	May 2008
Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental bivalirudin is to be administered as an 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.	Drug: Bivalirudin bivalirudin to be administered as an 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.
B: Active Comparator UFH given as an intravenous bolus of 140 units/kg. Double blinding will be maintained by using a double-dummy technique consisting of identical UFH and bivalirudin syringes and bivalirudin or placebo infusion bags.	Drug: Un-fractionated heparin UFH is given as an intravenous bolus of 140 units/kg followed by infusion of placebo 1.75 mg/kg per hour for the duration of the procedure.

Detailed Description:

Thrombin plays a major role in acute coronary artery occlusions during percutaneous coronary interventions.

Unfractionated heparin has been traditionally used during invasive coronary procedures to reduce the risk of thrombotic occlusion. Bivalirudin, a direct antithrombin inhibitor, has several advantages over unfractionated heparin: it acts independently of antithrombin and inhibits both free and clot-bound thrombin; it is not neutralized by circulating inhibitors; exhibits consistent dose-response characteristics, and does not cause thrombocytopenia. Previous studies have shown that use of bivalirudin among patients undergoing percutaneous coronary interventions is associated with better outcomes (death, myocardial infarction, urgent repeat revascularization or in-hospital major bleeding) as compared with unfractionated heparin and adjunctive use of glycoprotein IIb/IIIa platelet receptor inhibitors. However, previous studies have included patients treated with plain balloon angioplasty or stenting after inadequate pre-treatment with thienopyridines (ticlopidine or clopidogrel). Recent guidelines recommend that all patients undergoing percutaneous coronary interventions must receive a loading dose of 300 -600 mg of clopidogrel. A 600 mg loading dose of clopidogrel eliminates the need for glycoprotein IIb/IIIa platelet receptor inhibitors in adjunct to heparin. According to existing evidence antithrombotic regimens based on either bivalirudin or pre-treatment with 600 mg of clopidogrel in addition to UFH intraprocedurally, are effective strategies to reduce ischemic and hemorrhagic complications in patients with coronary artery disease undergoing PCI. At present, it is not known whether bivalirudin is superior to UHF in patients who have been optimally pre-treated with a loading dose of clopidogrel.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients older than 18 years of age to undergo PCI
Clopidogrel loading at least 2 hrs prior to PCI according to the PCI guidelines
Informed, written consent

Exclusion Criteria:

Recent ST-elevation myocardial infarction within the last 48 hours
Cardiogenic shock
ACS and positive biomarkers (Troponin T > 0.03 µg/L)
Malignancies or other comorbid conditions (for example severe liver, renal and pancreatic disease) 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 within the last 6 weeks
Presence of diseases which have a high probability of vascular lesions and subsequent bleeding such as active gastric ulcer or active ulcerous colitis
Recent trauma or major surgery in the last month
Ophthalmic surgery or brain surgery in the last month
Retinopathies or vitreous body bleeding in the last month
History of intracranial bleeding or structural abnormalities (for example aneurysm of cerebral arteries)
Suspected aortic dissection; pericarditis and subacute bacterial endocarditis
Patient's refusal to blood transfusion
Oral anticoagulation therapy with coumarin derivative within the last 7 days
Treatment with UFH within 6 hours or low-molecular weight heparin within 8 hours before randomization
Treatment with bivalirudin within 24 hours before randomization
Severe uncontrolled hypertension >180/110 mmHg unresponsive to therapy
Planned staged PCI procedure within 30 days from index procedure or prior PCI within the last 30 days
Relevant hematologic deviations:hemoglobin < 100 g/L; platelet count < 100 x 109 /L
Glomerular filtration rate (GFR) < 30 ml/min or serum creatinine > 30 mg/L or dependence on renal dialysis
Known allergy to the study medications: aspirin, clopidogrel, UFH, bivalirudin; stainless steel; true anaphylaxis after prior exposure to contrast media
Known heparin-induced thrombocytopenia (Typ II)
Previous enrollment in this trial
Pregnancy (present, suspected or planned) or positive pregnancy test
Spinal, peridural and epidural anesthesia
Patient's inability to fully cooperate with the study protocol

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00262054

Locations

Germany
Deutsches Herzzentrum Muenchen
Munich, Germany, 80636
First Medizinische Klinik, Klinikum rechts der Isar
Munich, Germany, 81675
Herz-Zentrum
Bad Krozingen, Germany, 79189
Segeberger Kliniken
Bad Segeberg, Germany, 23795

Sponsors and Collaborators

Deutsches Herzzentrum Muenchen

Investigators

Study Chair:	Albert Schomig, MD	Deutsches Herzzentrum Muenchen
Principal Investigator:	Adnan Kastrati, MD	Deutsches Herzzentrum Muenchen
Study Director:	Franz-Josef Neumann, MD	Herz-Zentrum Bad Krozingen

More Information

Publications:

Verstraete M. Direct thrombin inhibitors: appraisal of the antithrombotic/hemorrhagic balance. Thromb Haemost. 1997 Jul;78(1):357-63. Review. No abstract available.

Lincoff AM, Bittl JA, Harrington RA, Feit F, Kleiman NS, Jackman JD, Sarembock IJ, Cohen DJ, Spriggs D, Ebrahimi R, Keren G, Carr J, Cohen EA, Betriu A, Desmet W, Kereiakes DJ, Rutsch W, Wilcox RG, de Feyter PJ, Vahanian A, Topol EJ; REPLACE-2 Investigators. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. JAMA. 2003 Feb 19;289(7):853-63. Erratum in: JAMA. 2003 Apr 2;289(13):1638.

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, 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.

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Kastrati A, Neumann FJ, Mehilli J, Byrne RA, Iijima R, Büttner HJ, Khattab AA, Schulz S, Blankenship JC, Pache J, Minners J, Seyfarth M, Graf I, Skelding KA, Dirschinger J, Richardt G, Berger PB, Schömig A; the ISAR-REACT 3 Trial Investigators. Bivalirudin versus Unfractionated Heparin during Percutaneous Coronary Intervention. N Engl J Med. 2008 Aug 14;359(7):688-696.

Responsible Party:	Deutsches Herzzentrum Munich ( Prof. A. Schömig )
Study ID Numbers:	GE IDE No. A01005, KKF 1.1-05
Study First Received:	December 5, 2005
Last Updated:	August 26, 2008
ClinicalTrials.gov Identifier:	NCT00262054 History of Changes
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Deutsches Herzzentrum Muenchen:

coronary disease

Study placed in the following topic categories:

Arterial Occlusive Diseases
Anticoagulants
Heart Diseases
Heparin, Low-Molecular-Weight
Myocardial Ischemia
Angina Pectoris
Vascular Diseases
Abciximab
Fibrinolytic Agents
Pain
Cardiovascular Agents

Ischemia
Arteriosclerosis
Chest Pain
Calcium heparin
Coronary Disease
Signs and Symptoms
Fibrin Modulating Agents
Bivalirudin
Heparin
Coronary Artery Disease

Additional relevant MeSH terms:

Arterial Occlusive Diseases
Anticoagulants
Heart Diseases
Molecular Mechanisms of Pharmacological Action
Heparin, Low-Molecular-Weight
Myocardial Ischemia
Hematologic Agents
Angina Pectoris
Vascular Diseases
Fibrinolytic Agents
Pain
Cardiovascular Agents

Arteriosclerosis
Pharmacologic Actions
Chest Pain
Coronary Disease
Signs and Symptoms
Fibrin Modulating Agents
Therapeutic Uses
Bivalirudin
Cardiovascular Diseases
Heparin
Coronary Artery Disease

ClinicalTrials.gov processed this record on August 30, 2009