Clinical trial NCT00004562: Occluded Artery Trial (OAT)
Official title: Occluded Artery Trial (OAT) - Randomized Comparative Effectiveness Trial of PCI and Medical Therapy Only Post MI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiovascular Diseases
Heart Diseases
Myocardial Infarction
Heart Failure, Congestive
Heart Failure
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2000-02-10
Enrollment: 2201
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether opening an occluded infarcted artery 3-28 days after an acute myocardial infarction in high-risk asymptomatic patients reduces the composite endpoint of mortality, recurrent myocardial infarction, and hospitalization for class IV congestive heart failure over an average 2.9-year follow-up with extended follow up for an average of six years. Long term follow-up of patients were completed in March 2010. Final collection of all regulatory documentation was completed June 2011.

Detailed description: BACKGROUND:

The benefits of establishing early coronary reperfusion in acute myocardial infarction (MI) have now been unequivocally established. However, current pharmacologic strategies fail to achieve effective reperfusion in 30 percent or more of patients, and many patients with occluded infarct arteries do not meet current criteria for use of these agents. Early angioplasty, an effective reperfusion method, is available to a small proportion of potentially eligible US acute MI patients. Hence a substantial number of acute MI patients pass the time when reperfusion therapy has any documented benefit (12 - 24 hours) with a persistently closed infarct vessel. Several lines of experimental and clinical evidence suggest that late reperfusion of these patients could provide clinically significant reductions in mortality and morbidity.

DESIGN NARRATIVE:

Multicenter, randomized, controlled. Patients at 217 clinical sites in the United States, Canada and Internationally were randomly allocated to two treatment arms over five years. One treatment consists of conventional medical management including aspirin, beta blockers, angiotensin converting enzyme (ACE) inhibitors, and risk factor modification. The other treatment consists of conventional medical therapy plus percutaneous coronary intervention and coronary stenting. Clinical outcomes will be compared using an intention-to-treat analysis. The primary composite endpoint is mortality, recurrent myocardial infarction, and hospitalization for NYHA Class IV congestive heart failure over a three year follow-up. Individual components of the study composite primary endpoint will be compared in the two treatment arms, as will the medical costs of the two treatments and the health-related quality of life. The cost-effectiveness of percutaneous revascularization will be assessed in the study population.

Eligibility criteria: Inclusion Criteria:

* Recent MI (3-28 days) (Day 1 is the calendar day of the MI system onset)
* MI is defined based on at least 2 of 3 MI criteria confirmed by: 1) ischemic symptoms ≥30 minutes, 2) cardiac serum marker elevation (creatine kinase (CK) ≥2x upper limit of normal and CK-MB elevated above the upper limit of the laboratory normal) or troponin T, or troponin I elevated at least twice the upper limit of normal, 3) EKG: New Q-waves of ≥0.03 sec and/or 1/3 of QRS complex in ≥2 related EKG leads. If cardiac serum markers are elevated (2), any one of the following EKG findings satisfy inclusion criteria; new ST-T changes (ST elevation or depression), new left bundle-branch block (LBBB), loss of R-wave voltage ≥50% in ≥2 related leads or deep T wave inversions ≥3mm in ≥2 leads.
* TIMI flow 0 or 1 in infarct related artery (IRA)
* Meets criteria for high risk: EF \<50% or site of occlusion is proximal, in left anterior descending (proximal to the second major diagonal branch); large right coronary artery; or circumflex, if supplying large obtuse marginal, and part of inferior wall (i.e., large dominant or co-dominant vessel).

Exclusion Criteria:

* Age \<18 y
* Clinical indication for revascularization defined as follows: rest or low-threshold angina after MI; severe inducible ischemia on low level exercise or pharmacological stress testing (ST decreased ≥2 mm or inability to complete stage 1 or achieve 3-4 metabolic equivalents without angina, hypotension, or reversible perfusion defects in multiple territories or decreased wall motion thickening in \>2 segments on echocardiogram); left main coronary disease (≥50% stenosis); or triple-vessel disease (3 major epicardial coronaries with \>70% stenoses)
* Serious illness such as cancer or pulmonary disease that limits 3-year survival
* Severe renal disease defined as serum creatinine \>3.0 mg/dL that markedly increases risk of radiographic contrast
* Severe valvular disease
* History of anaphylaxis to radiographic contrast
* Infarct artery too small (reference segment diameter \<2.5 mm), target segment within or beyond extreme tortuosity (\>90° angulation), or otherwise technically a poor candidate for PCI
* Chronic occlusion of IRA (seen on angiogram obtained before index MI or angiographic evidence of chronicity, e.g., presence of bridging collaterals)
* NYHA classes III-IV CHF; patients may be treated for acute heart failure complicating MI and rescreened
* Cardiogenic shock or sustained hypotension: systolic BP \<90 mm Hg or cardiac index \<2.2 L/min per m\^2
* LV aneurysm in the same location as index MI and present before index MI
* Inability to cooperate with the protocol
* Patient refusal or inability to give informed consent
* Refusal of patient's physician to allow patient to participate
* Pregnancy
* Contraindication to anticoagulation during PCI or to routine antiplatelet therapy after stent implantation
* Qualifying IRA that has been grafted previously; patients with prior CABG may be enrolled if the IRA was not previously grafted
* Dilated or hypertrophic cardiomyopathy

Primary outcomes:
measure: Number of Patients That Had a First Occurrence of the Primary End Point (Composite of Death From Any Cause, Nonfatal MI, or Class IV HF)
timeFrame: Measured over a maximum 9-year follow-up period - 6 year median
Secondary outcomes:
measure: Number of Participants With Secondary Outcomes (Safety Events)
timeFrame: Measured over a maximum 9-year follow-up period - 6 year median
Other outcomes:
Locations:
city: New York
country: United States
facility: New York University School of Medicine
state: New York
Study officials:
affiliation: NYU Langone Health
name: Judith S. Hochman, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hochman JS, Lamas GA, Knatterud GL, Buller CE, Dzavik V, Mark DB, Reynolds HR, White HD; Occluded Artery Trial Research Group. Design and methodology of the Occluded Artery Trial (OAT). Am Heart J. 2005 Oct;150(4):627-42. doi: 10.1016/j.ahj.2005.07.002.
citation: Skolnick AH, Reynolds HR, White HD, Menon V, Carvalho AC, Maggioni AP, Pearte CA, Gruberg L, Azevedo RE, Schroeder E, Forman SA, Lamas GA, Hochman JS, Dzavik V. Comparison of late results of percutaneous coronary intervention among stable patients </=65 versus >65 years of age with an occluded infarct related artery (from the Occluded Artery Trial). Am J Cardiol. 2012 Mar 1;109(5):614-9. doi: 10.1016/j.amjcard.2011.10.015. Epub 2011 Dec 14.
citation: Deyell MW, Buller CE, Miller LH, Wang TY, Dai D, Lamas GA, Srinivas VS, Hochman JS. Impact of National Clinical Guideline recommendations for revascularization of persistently occluded infarct-related arteries on clinical practice in the United States. Arch Intern Med. 2011 Oct 10;171(18):1636-43. doi: 10.1001/archinternmed.2011.315. Epub 2011 Jul 11.
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citation: Devlin G, Reynolds HR, Mark DB, Rankin JM, Carvalho AC, Vozzi C, Sopko G, Caramori P, Dzavik V, Ragosta M, Forman SA, Lamas GA, Hochman JS. Loss of short-term symptomatic benefit in patients with an occluded infarct artery is unrelated to non-protocol revascularization: results from the Occluded Artery Trial (OAT). Am Heart J. 2011 Jan;161(1):84-90. doi: 10.1016/j.ahj.2010.09.009.
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citation: Malek LA, Reynolds HR, Forman SA, Vozzi C, Mancini GB, French JK, Dziarmaga M, Renkin JP, Kochman J, Lamas GA, Hochman JS. Late coronary intervention for totally occluded left anterior descending coronary arteries in stable patients after myocardial infarction: Results from the Occluded Artery Trial (OAT). Am Heart J. 2009 Apr;157(4):724-32. doi: 10.1016/j.ahj.2008.12.008.
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citation: Rashba EJ, Lamas GA, Couderc JP, Hollist SM, Dzavik V, Ruzyllo W, Fridrich V, Buller CE, Forman SA, Kufera JA, Carvalho AC, Hochman JS; OAT-EP Investigators. Electrophysiological effects of late percutaneous coronary intervention for infarct-related coronary artery occlusion: the Occluded Artery Trial-Electrophysiological Mechanisms (OAT-EP). Circulation. 2009 Feb 17;119(6):779-87. doi: 10.1161/CIRCULATIONAHA.108.808626. Epub 2009 Feb 2.
citation: Menon V, Pearte CA, Buller CE, Steg PG, Forman SA, White HD, Marino PN, Katritsis DG, Caramori P, Lasevitch R, Loboz-Grudzien K, Zurakowski A, Lamas GA, Hochman JS. Lack of benefit from percutaneous intervention of persistently occluded infarct arteries after the acute phase of myocardial infarction is time independent: insights from Occluded Artery Trial. Eur Heart J. 2009 Jan;30(2):183-91. doi: 10.1093/eurheartj/ehn486. Epub 2008 Nov 21.
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citation: Xing Z, Pei J, Huang J, Hu X, Gao S. Relationship of obesity to adverse events in myocardial infarction patients without primary percutaneous coronary intervention: results from the Occluded Artery Trial (OAT). Curr Med Res Opin. 2019 Sep;35(9):1563-1569. doi: 10.1080/03007995.2019.1603993. Epub 2019 May 10.
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