Un-fractionated Heparin Versus Bivalirudin During Percutaneous Coronary Interventions (PCI) (ISAR-REACT-3)

NCT00262054 | Completed Phase 4 DMC

• 2 other identifiers: GE IDE No. A01005KKF 1.1-05
• Study Type: interventional
• Target: 4,570
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Coronary Disease; Angina Pectoris

Keywords

coronary disease

Outcome Measures

Primary Outcomes (1)

• Composite rate of death, myocardial infarction (MI),urgent target vessel revascularization (TVR) within 30 days or in-hospital major bleeding

  30 days

Secondary Outcomes (2)

• Composite rate of death, MI or urgent TVR within 30 days

  30 days

• Composite rate of death, MI or TVR at 1 year

  1 year

Study Arms (2)

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

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

Interventions

Bivalirudin DRUG

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.

Also known as: ReoPro

A

Un-fractionated heparin DRUG

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.

B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Deutsches Herzzentrum Muenchen: lead

Study Sites (4)

Herz-Zentrum

Bad Krozingen, 79189, Germany

Location

Segeberger Kliniken

Bad Segeberg, 23795, Germany

Location

Deutsches Herzzentrum Muenchen

Munich, 80636, Germany

Location

First Medizinische Klinik, Klinikum rechts der Isar

Munich, 81675, Germany

Location

Related Publications (6)

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

  PMID: 9198179 BACKGROUND

• 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. doi: 10.1001/jama.289.7.853.

  PMID: 12588269 BACKGROUND

• 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. doi: 10.1093/eurheartj/ehi138. Epub 2005 Mar 15.

  PMID: 15769784 BACKGROUND

• 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.

  PMID: 14724302 BACKGROUND

• Schulz S, Mehilli J, Ndrepepa G, Neumann FJ, Birkmeier KA, Kufner S, Richardt G, Berger PB, Schomig A, Kastrati A; Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 3 Trial Investigators. Bivalirudin vs. unfractionated heparin during percutaneous coronary interventions in patients with stable and unstable angina pectoris: 1-year results of the ISAR-REACT 3 trial. Eur Heart J. 2010 Mar;31(5):582-7. doi: 10.1093/eurheartj/ehq008. Epub 2010 Feb 11.

  PMID: 20150324 RESULT

• Kastrati A, Neumann FJ, Mehilli J, Byrne RA, Iijima R, Buttner HJ, Khattab AA, Schulz S, Blankenship JC, Pache J, Minners J, Seyfarth M, Graf I, Skelding KA, Dirschinger J, Richardt G, Berger PB, Schomig A; ISAR-REACT 3 Trial Investigators. Bivalirudin versus unfractionated heparin during percutaneous coronary intervention. N Engl J Med. 2008 Aug 14;359(7):688-96. doi: 10.1056/NEJMoa0802944.

  PMID: 18703471 RESULT

MeSH Terms

Conditions

Coronary Disease; Angina Pectoris

Interventions

bivalirudin; Abciximab

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Albert Schomig, MD

  Deutsches Herzzentrum Muenchen

  STUDY CHAIR

• Adnan Kastrati, MD

  Deutsches Herzzentrum Muenchen

  PRINCIPAL INVESTIGATOR

• Franz-Josef Neumann, MD

  Herz-Zentrum Bad Krozingen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 5, 2005
• First Posted: December 6, 2005
• Study Start: November 1, 2005
• Primary Completion: February 1, 2008
• Study Completion: May 1, 2008
• Last Updated: March 15, 2010

Record last verified: 2008-08

Locations

DE (4)