NCT00373451

Brief 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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,721

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Jul 2006

Longer than P75 for phase_4

Geographic Reach
2 countries

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2006

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

September 7, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 8, 2006

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2011

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2011

Completed
Last Updated

May 8, 2012

Status Verified

May 1, 2012

Enrollment Period

4.8 years

First QC Date

September 7, 2006

Last Update Submit

May 7, 2012

Conditions

Myocardial InfarctionCoronary Disease

Keywords

NSTEMI

Outcome Measures

Primary Outcomes (1)

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

    30 days

Secondary Outcomes (2)

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

    30 days

  • Major bleedings

    30 days

Study Arms (2)

Abciximab+UFH

EXPERIMENTAL

Abciximab and unfractionated heparin as bolus given during PCI and abciximab-perfusion for 12 hours after PCI

Drug: Abciximab + UFHDrug: Heparin

Bivalirudin

ACTIVE COMPARATOR

Bivalirudin given only during PCI

Drug: Bivalirudin

Interventions

Abciximab + UFHDRUG

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)

Also known as: ReoPro
Abciximab+UFH
BivalirudinDRUG

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)

Also known as: Angiox
Bivalirudin
HeparinDRUG

i.v. bolus of 70 units/kg/body weight of unfractionated heparin

Also known as: unfractionated heparin
Abciximab+UFH

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Episode of unstable angina
  • Elevated cardiac markers
  • Angiographic lesions requiring PCI
  • Informed, written consent

You may not qualify if:

  • 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
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Herz-Zentrum Bad Krozingen

Bad Krozingen, 79189, Germany

Location

Herz- und Gefaessklinik, Kardiologie

Bad Neustadt an der Saale, 97616, Germany

Location

Vivantes Klinikum im Friedrichshain

Berlin, 10249, Germany

Location

Vivantes Auguste Viktoria Klinikum

Berlin, 12157, Germany

Location

Vivantes Klinikum Neukoelln

Berlin, 12351, Germany

Location

Deutsches Herzzentrum Muenchen

Munich, 80636, Germany

Location

Medizinische Klinik, Klinikum rechts der Isar

München, 81675, Germany

Location

Marienhospital Osnabrueck

Osnabrück, 49074, Germany

Location

Ospedale Cageggi

Florence, 50134, Italy

Location

Related Publications (11)

  • 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. doi: 10.1016/s0735-1097(02)02336-7. No abstract available.

    PMID: 12383588BACKGROUND

  • Schulman SP. Antiplatelet therapy in non-ST-segment elevation acute coronary syndromes. JAMA. 2004 Oct 20;292(15):1875-82. doi: 10.1001/jama.292.15.1875.

    PMID: 15494586BACKGROUND

  • 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.

    PMID: 14506118BACKGROUND

  • 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: 15769784BACKGROUND

  • 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.

    PMID: 16533938BACKGROUND

  • Mehilli J, Neumann FJ, Ndrepepa G, King L, Schulz S, Maimer Rodrigues da Cunha F, Jochheim D, Byrne RA, Hausleiter J, Ott I, Massberg S, Kastrati A, Pache J. Sex-related effectiveness of bivalirudin versus abciximab and heparin in non-ST-segment elevation myocardial infarction. Am Heart J. 2013 Apr;165(4):537-43. doi: 10.1016/j.ahj.2012.12.021. Epub 2013 Feb 19.

    PMID: 23537970DERIVED

  • Schulz S, Kastrati A, Ferenc M, Massberg S, Birkmeier KA, Laugwitz KL, Kufner S, Gick M, Dommasch M, Schuhlen H, Schomig A, Berger PB, Mehilli J, Neumann FJ; Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 4 Trial Investigators. One-year outcomes with abciximab and unfractionated heparin versus bivalirudin during percutaneous coronary interventions in patients with non-ST-segment elevation myocardial infarction: updated results from the ISAR-REACT 4 trial. EuroIntervention. 2013 Aug 22;9(4):430-6. doi: 10.4244/EIJV9I4A71.

    PMID: 23455033DERIVED

  • Ndrepepa G, Neumann FJ, Deliargyris EN, Mehran R, Mehilli J, Ferenc M, Schulz S, Schomig A, Kastrati A, Stone GW. Bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor in patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention after clopidogrel pretreatment: pooled analysis from the ACUITY and ISAR-REACT 4 trials. Circ Cardiovasc Interv. 2012 Oct;5(5):705-12. doi: 10.1161/CIRCINTERVENTIONS.112.972869. Epub 2012 Oct 9.

    PMID: 23048052DERIVED

  • Sibbing D, Bernlochner I, Schulz S, Massberg S, Schomig A, Mehilli J, Kastrati A. The impact of smoking on the antiplatelet action of clopidogrel in non-ST-elevation myocardial infarction patients: results from the ISAR-REACT 4 platelet substudy. J Thromb Haemost. 2012 Oct;10(10):2199-202. doi: 10.1111/j.1538-7836.2012.04867.x. No abstract available.

    PMID: 22845802DERIVED

  • Sibbing D, Bernlochner I, Schulz S, Massberg S, Schomig A, Mehilli J, Kastrati A. Prognostic value of a high on-clopidogrel treatment platelet reactivity in bivalirudin versus abciximab treated non-ST-segment elevation myocardial infarction patients. ISAR-REACT 4 (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment-4) platelet substudy. J Am Coll Cardiol. 2012 Jul 31;60(5):369-77. doi: 10.1016/j.jacc.2012.02.044. Epub 2012 Jun 6.

    PMID: 22682553DERIVED

  • Kastrati A, Neumann FJ, Schulz S, Massberg S, Byrne RA, Ferenc M, Laugwitz KL, Pache J, Ott I, Hausleiter J, Seyfarth M, Gick M, Antoniucci D, Schomig A, Berger PB, Mehilli J; ISAR-REACT 4 Trial Investigators. Abciximab and heparin versus bivalirudin for non-ST-elevation myocardial infarction. N Engl J Med. 2011 Nov 24;365(21):1980-9. doi: 10.1056/NEJMoa1109596. Epub 2011 Nov 13.

    PMID: 22077909DERIVED

MeSH Terms

Conditions

Myocardial InfarctionCoronary DiseaseNon-ST Elevated Myocardial Infarction

Interventions

AbciximabbivalirudinHeparin

Condition Hierarchy (Ancestors)

Myocardial IschemiaHeart DiseasesCardiovascular DiseasesVascular DiseasesInfarctionIschemiaPathologic ProcessesPathological Conditions, Signs and SymptomsNecrosis

Intervention Hierarchy (Ancestors)

Immunoglobulin Fab FragmentsImmunoglobulin FragmentsPeptide FragmentsPeptidesAmino Acids, Peptides, and ProteinsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsSerum GlobulinsGlobulinsGlycosaminoglycansPolysaccharidesCarbohydrates

Study Officials

  • Albert Schoemig, MD

    Deutsches Herzzentrum Muenchen

    STUDY CHAIR

  • Adnan Kastrati, MD

    Deutsches Herzzentrum Muenchen

    PRINCIPAL INVESTIGATOR

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
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 7, 2006

First Posted

September 8, 2006

Study Start

July 1, 2006

Primary Completion

May 1, 2011

Study Completion

July 1, 2011

Last Updated

May 8, 2012

Record last verified: 2012-05

Locations

IT(1)DE(8)