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Myocardial InfarctionPhase 3NCT00433966

Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction

A Phase 3 study testing Bivalirudin, Unfractionated heparin and Bare metal stent in people with Myocardial Infarction, run by Cardiovascular Research Foundation, New York at 1 site in United States.

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 primary objectives of the trial are: 1. To establish the safety and efficacy of the use of bivalirudin (+ bail-out GP IIb/IIIa inhibitors) compared to the use of unfractionated heparin + GP IIb/IIIa inhibitors in patients with acute myocardial infarction undergoing a primary angioplasty strategy. 2. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myocardial Infarction
What is being tested?
Bivalirudin, Unfractionated heparin and Bare metal stent
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3,602 participants
Where
1 siteUnited States
Study dates
Mar 2005to Nov 2010
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Must have clinical symptoms consistent with AMI (e.g., angina or anginal equivalent)lasting >20 minutes but <12 hours in duration;
  • ST-segment elevation of >1 mm in >2 contiguous leads, or (presumably new) left bundle branch block, or true posterior MI with ST depression of >1 mm in >2 contiguous anterior leads;
  • The patient or guardian agrees to the study protocol and the schedule of clinical and angiographic follow-up, and provides informed, written consent.

Who cannot join

  • The patient has a known hypersensitivity or contraindication to any of the following medications:
  • Heparin, pork or pork products
  • Both abciximab and eptifibatide
  • Aspirin
  • Both Clopidogrel and Ticlopidine
  • Bivalirudin
Show all 25Show fewer
  • Paclitaxel or Taxol
  • The polymer components of the TAXUS™ stent (SIBS)
  • Stainless steel and/or
  • Contrast media;
  • Prior administration of thrombolytic therapy, bivalirudin, GP IIb/IIIa inhibitors, low molecular weight heparin or fondaparinux for this admission. Patients receiving prior unfractionated heparin may be enrolled, and treated per randomization;
  • Current use of coumadin;
  • Systemic (intravenous) Paclitaxel or Taxol use within 12 months;
  • Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plans to become pregnant any time after enrollment into this study;
  • History of bleeding diathesis or known coagulopathy (including heparin-induced thrombocytopenia), or will refuse blood transfusions;
  • History of intra-cerebral mass, aneurysm, arteriovenous malformation, or hemorrhagic stroke;
  • Stroke or transient ischemic attack within the past 6 months, or any permanent residual neurologic defect;
  • Gastrointestinal or genitourinary bleeding within the last 2 months, or major surgery within six weeks;
  • Recent history or known current platelet count <100,000 cells/mm3 or Hgb <10 g/dL;
  • Extensive peripheral vascular disease, such that emergent angiography and intervention in the opinion of the investigator is likely to be difficult or complicated;
  • An elective surgical procedure is planned that would necessitate interruption of thienopyridines during the first six months post enrollment;
  • Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance;
  • Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period;
  • Previous enrollment in this trial;
  • Patients who underwent coronary stent implantation within the past 30 days.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • LeBauer CV Research Foundation

    Greensboro, North Carolina, 27401

Other trials in United States

About this study

Official title: Dual Arm Factorial Randomized Trial in Patients w/ST Segment Elevation AMI to Compare the Results of Using Anticoagulation With Either Unfractionated Heparin + Routine GP IIb/IIIa Inhibition or Bivalirudin + Bail-out GP IIb/IIIa Inhibition; and Primary Angioplasty With Stent Implantation With Either a Slow Rate-release Paclitaxel-eluting Stent (TAXUS™) or Uncoated Bare Metal Stent (EXPRESS2™)

The primary objectives of the trial are:

  1. To establish the safety and efficacy of the use of bivalirudin (+ bail-out GP IIb/IIIa inhibitors) compared to the use of unfractionated heparin + GP IIb/IIIa inhibitors in patients with acute myocardial infarction undergoing a primary angioplasty strategy.
  2. To establish the safety and efficacy of the slow rate release paclitaxel-eluting TAXUS™ stent compared to an otherwise identical uncoated bare metal EXPRESS2™ stent.
Read the detailed description

Prospective, 2 x 2 factorial single blind, randomized, multi-center trial of 3400 patients enrolled at up to 200 centers. Patients will be randomized 1:1 in the emergency room to a) anticoagulation with unfractionated heparin plus routine GP IIb/IIIa inhibition vs. b) bivalirudin and bail-out GP IIb/IIIa inhibition. Following angiography, patients with lesions eligible for stenting will then undergo a second randomization (3:1) to stent implantation with either a) a slow rate-release paclitaxel-eluting stent (TAXUS™) or b) an otherwise identical uncoated bare metal stent (EXPRESS2™).

Being tested
Bivalirudin, Unfractionated heparin, Bare metal stent, Paclitaxel-eluting stent
Keywords
Myocardial Infarction, Angioplasty, Myocardial Ischemia, Myocardial Reperfusion, Stents, Heart Disease
Medical subject headings
Myocardial Infarction, Myocardial Ischemia, Heart Diseases

What participants receive

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

  • BivalirudinDrug

    Also called Angiomax

    Bivalirudin bolus of 0.75 mg/kg IV, followed by an infusion of 1.75 mg/kg/h as soon as logistically feasible (ideally in the emergency room).

  • Unfractionated heparinDrug

    Also called Heparin Sodium

    60 U/kg of IV heparin, started as soon as possible (ideally in the emergency room).

  • Bare metal stentDevice

    Also called EXPRESS2™

    Uncoated bare metal stent

  • Paclitaxel-eluting stentDevice

    Also called TAXUS™

    slow rate-release paclitaxel-eluting stent

Study groups in NCT00433966
Study groupRoleWhat they receive
Pharmacology ArmActive comparatorTo establish the safety and efficacy of the use of bivalirudin in patients with acute myocardial infarction undergoing a primary angioplasty strategy by showing that compared to unfractionated heparin plus routine use of GP IIb/IIIa inhibitors, bivalirudin (with use of GP IIb/IIIa inhibitors reserved for angioplasty complications) results in: 1. reduced rates of major bleeding events at 30 days 2. similar rates of major adverse ischemic cardiac events at 30 days 3. reduced rates of the composite of major adverse ischemic cardiac events + major bleeding at 30 days.
Receives: Drug: Bivalirudin; Drug: Unfractionated heparin
Stent ArmActive comparatorTo establish the safety and efficacy of the paclitaxel-eluting TAXUS™ stent by showing that compared to an otherwise identical bare metal EXPRESS2™ stent, the TAXUS™ stent results in: 1. reduced rates of target lesion revascularization for ischemia at 1 year 2. similar rates of death, reinfarction, stroke or stent thrombosis at 1 year 3. lower rates of analysis segment binary angiographic restenosis at 13 months
Receives: Device: Bare metal stent; Device: Paclitaxel-eluting stent

What is being measured

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

  1. Pharmacology Arm - Major Adverse Ischemic Cardiac Events and Major Bleeding Events

    Number of participants with major adverse cardiovascular events (death, reinfarction, target-vessel revascularization for ischemia, and stroke) and major bleeding (bleeding adjudicated as not related to coronary artery bypass grafting).

    Measured: 30 Days

  2. Stent Arm - Ischemic Target Lesion Revascularization

    Number of Participants With Ischemic Target Lesion Revascularization

    Measured: 1 year

  3. Stent Arm - Death, Reinfarction, Stroke, or Stent Thrombosis

    Number of Participants With Death, Reinfarction, Stroke, or Stent Thrombosis

    Measured: 1 year

Secondary outcomes (4)

  1. Pharmacology Arm - Major Adverse Cardiovascular Events

    Number of participants with major adverse cardiovascular events (death, reinfarction, target-vessel revascularization for ischemia, and stroke)

    Measured: 30 days

  2. Pharmacology Arm - Non-Coronary Artery Bypass Grafting-Related Major Bleeding

    Number of participants with major bleeding (bleeding adjudicated as not related to coronary artery bypass grafting)

    Measured: 30 days

  3. Stent Arm - Segment Binary Angiographic Restenosis

    Number of Participants With Segment Binary Angiographic Restenosis (13-month Angiographic Subset).

    Measured: 13 months

  4. Pharmacology Arm - Major Adverse Cardiovascular Events

    Number of participants with major adverse cardiovascular events (death, reinfarction, target-vessel revascularization for ischemia, and stroke)

    Measured: 3 years

Timeline

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

  1. First posted12 Feb 2007 (estimated)
  2. Study startMar 2005
  3. Primary completionJun 2008
  4. Study completionNov 2010

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Masking
Single blind
Who is masked
Participant
Enrolment
3,602 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00433966
Sponsor's protocol ID
HORIZONS AMI
Status last verified
Nov 2017
First submitted
9 Feb 2007
Last updated
4 Dec 2017
Data monitoring committee
Yes

Publications

  • Kosmidou I, McAndrew T, Redfors B, Embacher M, Dizon JM, Mehran R, Ben-Yehuda O, Mintz GS, Stone GW. Correlation of Admission Heart Rate With Angiographic and Clinical Outcomes in Patients With Right Coronary Artery ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: HORIZONS-AMI (The Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) Trial. J Am Heart Assoc. 2017 Jul 19;6(7):e006181. doi: 10.1161/JAHA.117.006181.

    PubMed 28724652

  • Tamez H, Pinto DS, Kirtane AJ, Litherland C, Yeh RW, Dangas GD, Mehran R, Deliargyris EN, Ortiz G, Gibson CM, Stone GW. Effect of Short Procedural Duration With Bivalirudin on Increased Risk of Acute Stent Thrombosis in Patients With STEMI: A Secondary Analysis of the HORIZONS-AMI Randomized Clinical Trial. JAMA Cardiol. 2017 Jun 1;2(6):673-677. doi: 10.1001/jamacardio.2016.5669.

    PubMed 28249084

  • Ducrocq G, Steg PG, Van't Hof A, Zeymer U, Mehran R, Hamm CW, Bernstein D, Prats J, Deliargyris EN, Stone GW. Utility of post-procedural anticoagulation after primary PCI for STEMI: insights from a pooled analysis of the HORIZONS-AMI and EUROMAX trials. Eur Heart J Acute Cardiovasc Care. 2017 Oct;6(7):659-665. doi: 10.1177/2048872616650869. Epub 2016 Jun 10.

    PubMed 27287251

  • Dangas GD, Schoos MM, Steg PG, Mehran R, Clemmensen P, van 't Hof A, Prats J, Bernstein D, Deliargyris EN, Stone GW. Early Stent Thrombosis and Mortality After Primary Percutaneous Coronary Intervention in ST-Segment-Elevation Myocardial Infarction: A Patient-Level Analysis of 2 Randomized Trials. Circ Cardiovasc Interv. 2016 May;9(5):e003272. doi: 10.1161/CIRCINTERVENTIONS.115.003272.

    PubMed 27165710

  • Weisz G, Smilowitz NR, Kirtane AJ, Rinaldi MJ, Parvataneni R, Xu K, Stuckey TD, Maehara A, Witzenbichler B, Neumann FJ, Metzger DC, Henry TD, Cox DA, Duffy PL, Brodie BR, Mazzaferri EL Jr, Mehran R, Stone GW. Proton Pump Inhibitors, Platelet Reactivity, and Cardiovascular Outcomes After Drug-Eluting Stents in Clopidogrel-Treated Patients: The ADAPT-DES Study. Circ Cardiovasc Interv. 2015 Oct;8(10):e001952. doi: 10.1161/CIRCINTERVENTIONS.114.001952.

    PubMed 26458411

  • Giacoppo D, Madhavan MV, Baber U, Warren J, Bansilal S, Witzenbichler B, Dangas GD, Kirtane AJ, Xu K, Kornowski R, Brener SJ, Genereux P, Stone GW, Mehran R. Impact of Contrast-Induced Acute Kidney Injury After Percutaneous Coronary Intervention on Short- and Long-Term Outcomes: Pooled Analysis From the HORIZONS-AMI and ACUITY Trials. Circ Cardiovasc Interv. 2015 Aug;8(8):e002475. doi: 10.1161/CIRCINTERVENTIONS.114.002475.

    PubMed 26198286

  • Nikolsky E, Mehran R, Dangas GD, Xu K, Parvataneni R, Witzenbichler B, Guagliumi G, Kornowski R, Genereux P, Brener SJ, Stone GW. Cerebrovascular events after a primary percutaneous coronary intervention strategy for acute ST-segment-elevation myocardial infarction: analysis from the HORIZONS-AMI Trial. Circ Cardiovasc Interv. 2015 Apr;8(4):e002283. doi: 10.1161/CIRCINTERVENTIONS.114.002283.

    PubMed 25858976

  • Stone GW, Mehran R, Goldstein P, Witzenbichler B, Van't Hof A, Guagliumi G, Hamm CW, Genereux P, Clemmensen P, Pocock SJ, Gersh BJ, Bernstein D, Deliargyris EN, Steg PG. Bivalirudin versus heparin with or without glycoprotein IIb/IIIa inhibitors in patients with STEMI undergoing primary percutaneous coronary intervention: pooled patient-level analysis from the HORIZONS-AMI and EUROMAX trials. J Am Coll Cardiol. 2015 Jan 6;65(1):27-38. doi: 10.1016/j.jacc.2014.10.029.

    PubMed 25572507

  • Sanborn TA, Tomey MI, Mehran R, Genereux P, Witzenbichler B, Brener SJ, Kirtane AJ, McAndrew TC, Kornowski R, Dudek D, Nikolsky E, Stone GW. Femoral vascular closure device use, bivalirudin anticoagulation, and bleeding after primary angioplasty for STEMI: results from the HORIZONS-AMI trial. Catheter Cardiovasc Interv. 2015 Feb 15;85(3):371-9. doi: 10.1002/ccd.25663. Epub 2014 Oct 28.

    PubMed 25179260

  • Stone SG, Serrao GW, Mehran R, Tomey MI, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, Mockel M, Brener SJ, Dangas G, Stone GW. Incidence, predictors, and implications of reinfarction after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction: the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction Trial. Circ Cardiovasc Interv. 2014 Aug;7(4):543-51. doi: 10.1161/CIRCINTERVENTIONS.114.001360. Epub 2014 Jun 17.

    PubMed 24939928

  • Keeley EC, Mehran R, Brener SJ, Witzenbichler B, Guagliumi G, Dudek D, Kornowski R, Dressler O, Fahy M, Xu K, Grines CL, Stone GW. Impact of multiple complex plaques on short- and long-term clinical outcomes in patients presenting with ST-segment elevation myocardial infarction (from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI] Trial). Am J Cardiol. 2014 May 15;113(10):1621-7. doi: 10.1016/j.amjcard.2014.02.016. Epub 2014 Mar 1.

    PubMed 24703369

  • Larsen AI, Tomey MI, Mehran R, Nilsen DW, Kirtane AJ, Witzenbichler B, Guagliumi G, Brener SJ, Genereux P, Kornowski R, Dudek D, Gersh BJ, Stone GW. Comparison of outcomes in patients with ST-segment elevation myocardial infarction discharged on versus not on statin therapy (from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction Trial). Am J Cardiol. 2014 Apr 15;113(8):1273-9. doi: 10.1016/j.amjcard.2014.01.401. Epub 2014 Jan 31.

    PubMed 24576541

  • Genereux P, Madhavan MV, Mintz GS, Maehara A, Palmerini T, Lasalle L, Xu K, McAndrew T, Kirtane A, Lansky AJ, Brener SJ, Mehran R, Stone GW. Ischemic outcomes after coronary intervention of calcified vessels in acute coronary syndromes. Pooled analysis from the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) TRIALS. J Am Coll Cardiol. 2014 May 13;63(18):1845-54. doi: 10.1016/j.jacc.2014.01.034. Epub 2014 Feb 19.

    PubMed 24561145

  • Stone GW, Clayton T, Deliargyris EN, Prats J, Mehran R, Pocock SJ. Reduction in cardiac mortality with bivalirudin in patients with and without major bleeding: The HORIZONS-AMI trial (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction). J Am Coll Cardiol. 2014 Jan 7-14;63(1):15-20. doi: 10.1016/j.jacc.2013.09.027. Epub 2013 Oct 16.

    PubMed 24140664

  • Brener SJ, Dizon JM, Mehran R, Guerchicoff A, Lansky AJ, Farkouh M, Brodie B, Guagliumi G, Witzenbichler B, Fahy M, Parise H, Stone GW. Complementary prognostic utility of myocardial blush grade and ST-segment resolution after primary percutaneous coronary intervention: analysis from the HORIZONS-AMI trial. Am Heart J. 2013 Oct;166(4):676-83. doi: 10.1016/j.ahj.2013.07.025. Epub 2013 Sep 13.

    PubMed 24093847

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bivalirudin, Unfractionated heparin and Bare metal stent in people with Myocardial Infarction, run by Cardiovascular Research Foundation, New York at 1 site in United States.

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 3 inclusion and 25 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 4 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Pharmacology Arm - Major Adverse Ischemic Cardiac Events and Major Bleeding Events (time frame: 30 Days). The study lists 3 primary outcomes in all. 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 NCT00433966, which also lists 48 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 4 Dec 2017.

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