Current partner codePEPTIDESDE
NCT00433966·Phase 3·INTERVENTIONAL

Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction

Status

Completed

Phase

Phase 3

Enrollment

3,602

Locations

1

Results

Posted

Publications

12

Study summary

What the protocol is testing.

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.

Full 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™).

Interventions

Treatment arms and agents.

DRUG

Bivalirudin

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).

DRUG

Unfractionated heparin

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

DEVICE

Bare metal stent

Uncoated bare metal stent

DEVICE

Paclitaxel-eluting stent

slow rate-release paclitaxel-eluting stent

Timeline

From registration to results.

  1. First posted

    Feb 12, 2007

  2. Study start

    Mar 2005

  3. Primary completion

    Jun 2008

  4. Study completion

    Nov 2010

  5. Results posted

    Dec 4, 2017

  6. Registry updated

    Dec 4, 2017

Outcomes

What the study measures.

Primary outcomes

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

Time frame · 30 Days

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).

Stent Arm - Ischemic Target Lesion Revascularization

Time frame · 1 year

Number of Participants With Ischemic Target Lesion Revascularization

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

Time frame · 1 year

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

Secondary outcomes

Pharmacology Arm - Major Adverse Cardiovascular Events

Time frame · 30 days

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

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

Time frame · 30 days

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

Stent Arm - Segment Binary Angiographic Restenosis

Time frame · 13 months

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

Pharmacology Arm - Major Adverse Cardiovascular Events

Time frame · 3 years

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

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
Not reported
Sex
ALL
Healthy volunteers
No

Inclusion Criteria: * 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. Exclusion Criteria: * 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 * 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.

Study locations

1 registered sites.

United States. Showing up to 24 locations stored in the fast local snapshot.

LeBauer CV Research Foundation

Greensboro, North Carolina, United States

Publications

Results and literature.

PMID 28724652Kosmidou 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.PMID 28249084Tamez 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.PMID 27287251Ducrocq 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.PMID 27165710Dangas 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.PMID 26458411Weisz 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.PMID 26198286Giacoppo 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.PMID 25858976Nikolsky 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.PMID 25572507Stone 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.PMID 25179260Sanborn 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.PMID 24939928Stone 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.PMID 24703369Keeley 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.PMID 24576541Larsen 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.

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