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Myocardial InfarctionPhase 4ISAR-REACT-4NCT00373451

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

A Phase 4 study testing Abciximab + UFH, Bivalirudin and Heparin in people with Myocardial Infarction and Coronary Disease, run by Deutsches Herzzentrum Muenchen at 9 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Myocardial Infarction, Coronary Disease
What is being tested?
Abciximab + UFH, Bivalirudin and Heparin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,721 participants
Where
9 sitesin 2 countries
Study dates
Jul 2006to Jul 2011
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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
Show all 18Show fewer
  • 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

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

Germany8 sites

  • Herz-Zentrum Bad Krozingen

    Bad Krozingen, 79189

  • Herz- und Gefaessklinik, Kardiologie

    Bad Neustadt an der Saale, 97616

  • Vivantes Klinikum im Friedrichshain

    Berlin, 10249

  • Vivantes Auguste Viktoria Klinikum

    Berlin, 12157

  • Vivantes Klinikum Neukoelln

    Berlin, 12351

  • Medizinische Klinik, Klinikum rechts der Isar

    München, 81675

  • Deutsches Herzzentrum Muenchen

    Munich, 80636

  • Marienhospital Osnabrueck

    Osnabrück, 49074

Other trials in Germany

Italy1 site

  • Ospedale Cageggi

    Florence, 50134

Other trials in Italy

About this study

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)

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.

Read the 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.

Being tested
Abciximab + UFH, Bivalirudin, Heparin
Keywords
NSTEMI
Medical subject headings
Myocardial Infarction, Coronary Disease, Non-ST Elevated Myocardial Infarction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Abciximab + UFHDrug

    Also called ReoPro

    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)

  • BivalirudinDrug

    Also called Angiox

    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)

  • HeparinDrug

    Also called unfractionated heparin

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

Study groups in NCT00373451
Study groupRoleWhat they receive
Abciximab+UFHExperimentalAbciximab and unfractionated heparin as bolus given during PCI and abciximab-perfusion for 12 hours after PCI
Receives: Drug: Abciximab + UFH; Drug: Heparin
BivalirudinActive comparatorBivalirudin given only during PCI
Receives: Drug: Bivalirudin

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 30 days

Secondary outcomes (2)

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

    Measured: 30 days

  2. Major bleedings

    Measured: 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Sep 2006 (estimated)
  2. Study startJul 2006
  3. Primary completionMay 2011
  4. Study completionJul 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,721 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00373451
Sponsor's protocol ID
GE IDE No. A01106
Acronym
ISAR-REACT-4
Status last verified
May 2012
First submitted
7 Sep 2006
Last updated
8 May 2012
Results posted
No
Data monitoring committee
Yes

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

    PubMed 12383588

  • 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.

    PubMed 15494586

  • 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.

    PubMed 14506118

  • 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.

    PubMed 15769784

  • 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.

    PubMed 16533938

  • 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.

    PubMed 23537970

  • 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.

    PubMed 23455033

  • 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.

    PubMed 23048052

  • 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.

    PubMed 22845802

  • 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.

    PubMed 22682553

  • 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.

    PubMed 22077909

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Abciximab + UFH, Bivalirudin and Heparin in people with Myocardial Infarction and Coronary Disease, run by Deutsches Herzzentrum Muenchen at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 May 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Germany, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite of death, large recurrent myocardial infarction (MI), urgent target vessel revascularization (TVR) or major bleeding (time frame: 30 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00373451, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2012.

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