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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01471522




Registration number
NCT01471522
Ethics application status
Date submitted
10/11/2011
Date registered
15/11/2011
Date last updated
1/06/2023

Titles & IDs
Public title
International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA)
Scientific title
International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA)
Secondary ID [1] 0 0
1U01HL105907
Secondary ID [2] 0 0
11-00498
Universal Trial Number (UTN)
Trial acronym
ISCHEMIA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiovascular Diseases 0 0
Coronary Disease 0 0
Coronary Artery Disease 0 0
Heart Diseases 0 0
Myocardial Ischemia 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - cardiac catheterization
Treatment: Surgery - coronary artery bypass graft surgery
Treatment: Surgery - percutaneous coronary intervention
Behaviour - Lifestyle
Treatment: Drugs - Medication

Active Comparator: Invasive Strategy (INV) - Routine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy.

Active Comparator: Conservative Strategy - Optimal medical therapy with cardiac catheterization and revascularization reserved for patients with acute coronary syndrome, ischemic heart failure, resuscitated cardiac arrest or refractory symptoms.


Treatment: Surgery: cardiac catheterization
Narrowed blood vessels can be opened without surgery using stents or can be bypassed with surgery. To determine which is the best approach for you the doctor needs to look at your blood vessels to see where the narrowings are and how much narrowing there is. This is done by a procedure known as a cardiac catheterization.

Treatment: Surgery: coronary artery bypass graft surgery
Artery narrowing is bypassed during surgery with a healthy artery or vein from another part of the body. This is known as coronary artery bypass grafting, or CABG (said, "cabbage"). The surgery creates new routes around narrowed and blocked heart arteries. This allows more blood flow to the heart.

Treatment: Surgery: percutaneous coronary intervention
Percutaneous coronary intervention may be done as part of the cardiac catheterization procedure. With this procedure a small, hollow, mesh tube (stent) is inserted into the narrowed part of the artery. The stent pushes the plaque against the artery wall, and opens the vessel to allow better blood flow.

Behaviour: Lifestyle
diet, physical activity, smoking cessation

Treatment: Drugs: Medication
antiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Behaviour
Intervention code [3] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Primary Composite Outcome: Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, Heart Failure, or Resuscitated Cardiac Arrest
Timepoint [1] 0 0
3.2 year follow-up (median)
Primary outcome [2] 0 0
Cumulative Event Rate of Primary Composite Outcome (Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, Heart Failure, or Resuscitated Cardiac Arrest)
Timepoint [2] 0 0
5 years
Primary outcome [3] 0 0
Number of Participants That Experienced Death From Cardiovascular Causes or Myocardial Infarction
Timepoint [3] 0 0
5 years
Primary outcome [4] 0 0
Cumulative Event Rate of Death From Cardiovascular Causes or Myocardial Infarction
Timepoint [4] 0 0
5 years
Primary outcome [5] 0 0
Number of Participants That Experienced Death From Any Cause
Timepoint [5] 0 0
5 years
Primary outcome [6] 0 0
Cumulative Event Rate of Death From Any Cause
Timepoint [6] 0 0
5 years
Primary outcome [7] 0 0
Number of Participants That Experienced Myocardial Infarction
Timepoint [7] 0 0
5 years
Primary outcome [8] 0 0
Cumulative Event Rate of Myocardial Infarction
Timepoint [8] 0 0
5 years
Primary outcome [9] 0 0
Estimated Difference in Cumulative Event Rate ( %) of Primary Composite Outcome: Invasive Minus Conservative
Timepoint [9] 0 0
5 years
Primary outcome [10] 0 0
Estimated Difference in Cumulative Event Rate of Death From Cardiovascular Causes: Invasive Minus Conservative or Myocardial Infarction Between Invasive and Conservative Strategies
Timepoint [10] 0 0
5 years
Primary outcome [11] 0 0
Estimated Difference in Cumulative Event Rate of Death From Any Cause: Invasive Minus Conservative
Timepoint [11] 0 0
5 years
Primary outcome [12] 0 0
Estimated Difference in Cumulative Event Rate of Myocardial Infarction: Invasive Minus Conservative
Timepoint [12] 0 0
5 years

Eligibility
Key inclusion criteria
- At least moderate ischemia on a qualifying stress test

- Participant is willing to comply with all aspects of the protocol, including adherence
to the assigned strategy, medical therapy and follow-up visits

- Participant is willing to give written informed consent

- Age = 21 years
Minimum age
21 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- LVEF < 35%

- History of unprotected left main stenosis >50% on prior coronary computed tomography
angiography (CCTA) or prior cardiac catheterization (if available)

- Finding of "no obstructive CAD" (<50% stenosis in all major epicardial vessels) on
prior CCTA or prior catheterization, performed within 12 months

- Coronary anatomy unsuitable for either PCI or CABG

- Unacceptable level of angina despite maximal medical therapy

- Very dissatisfied with medical management of angina

- History of noncompliance with medical therapy

- Acute coronary syndrome within the previous 2 months

- PCI within the previous 12 months

- Stroke within the previous 6 months or spontaneous intracranial hemorrhage at any time

- History of ventricular tachycardia requiring therapy for termination, or symptomatic
sustained ventricular tachycardia not due to a transient reversible cause

- NYHA class III-IV heart failure at entry or hospitalization for exacerbation of
chronic heart failure within the previous 6 months

- Non-ischemic dilated or hypertrophic cardiomyopathy

- End stage renal disease on dialysis or estimated glomerular filtration rate (eGFR)
<30mL/min (not an exclusion criterion for CKD ancillary trial, see CKD ancillary
trial, Section 18)

- Severe valvular disease or valvular disease likely to require surgery or percutaneous
valve replacement during the trial

- Allergy to radiographic contrast that cannot be adequately pre-medicated, or any prior
anaphylaxis to radiographic contrast

- Planned major surgery necessitating interruption of dual antiplatelet therapy (note
that patients may be eligible after planned surgery)

- Life expectancy less than the duration of the trial due to non-cardiovascular
comorbidity

- Pregnancy (known to be pregnant; to be confirmed before CCTA and/or randomization, if
applicable)

- Patient who, in the judgment of the patient's physician, is likely to have significant
unprotected left main stenosis (Those who are able to undergo CCTA will have visual
assessment of the left main coronary artery by the CCTA core lab)

- Enrolled in a competing trial that involves a non-approved cardiac drug or device

- Inability to comply with the protocol

- Exceeds the weight or size limit for CCTA or cardiac catheterization at the site

- Canadian Cardiovascular Society Class III angina of recent onset, OR angina of any
class with a rapidly progressive or accelerating pattern

- Canadian Cardiovascular Society Class IV angina, including unprovoked rest angina

- High risk of bleeding which would contraindicate the use of dual antiplatelet therapy

- Cardiac transplant recipient

- Prior CABG, unless CABG was performed more than 12 months ago, and coronary anatomy
has been demonstrated to be suitable for PCI or repeat CABG to accomplish complete
revascularization of ischemic areas (CCC approval required)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/05/2023
Sample size
Target
Accrual to date
Final
5179
Recruitment in Australia
Recruitment state(s)
NSW,SA,WA
Recruitment hospital [1] 0 0
John Hunter Hospital - New Lambton Heights
Recruitment hospital [2] 0 0
Flinders Medical Centre - Adelaide
Recruitment hospital [3] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [4] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [2] 0 0
5042 - Adelaide
Recruitment postcode(s) [3] 0 0
5011 - Woodville South
Recruitment postcode(s) [4] 0 0
6000 - Perth
Recruitment outside Australia
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Wroclaw
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Portugal
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Lisboa
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Lisbon
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Portugal
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Vila Nova de Gaia
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Romania
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Baia Mare
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Romania
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Bucharest
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Russian Federation
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Gorod Moskva
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Russian Federation
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Novosibirskaya Oblast
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Russian Federation
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Saint Petersburg
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Russian Federation
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Saint-Petersburg
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Saudi Arabia
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Central Province
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Serbia
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Vojvodina
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Serbia
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Belgrade
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Serbia
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Kragujevac
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Serbia
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Nis
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Singapore
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Singapore
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South Africa
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Western Cape
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Spain
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La Coruna
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A Coruna
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Barcelona
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Madrid
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Murcia
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Valencia
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Stockholm
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Uppsala
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Switzerland
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Ticino
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Taiwan
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Taipei City
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Thailand
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Meung
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Thailand
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Bangkok
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United Kingdom
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Antrim
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Bedfordshire
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Berdfordshire
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Cambridgeshire
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Cambs
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Cleveland
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Dorset
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East Yorkshire
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Essex
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Hampshire
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Lancashire
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West Midlands
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West Yorkshire
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United Kingdom
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London
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United Kingdom
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Manchester

Funding & Sponsors
Primary sponsor type
Other
Name
NYU Langone Health
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
New York University
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Stanford University
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Government body
Name [3] 0 0
National Heart, Lung, and Blood Institute (NHLBI)
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Government body
Name [4] 0 0
Albany Stratton VA Medical Center
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Cedars-Sinai Medical Center
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Columbia University
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
Duke University
Address [7] 0 0
Country [7] 0 0
Other collaborator category [8] 0 0
Other
Name [8] 0 0
East Carolina University
Address [8] 0 0
Country [8] 0 0
Other collaborator category [9] 0 0
Other
Name [9] 0 0
Emory University
Address [9] 0 0
Country [9] 0 0
Other collaborator category [10] 0 0
Other
Name [10] 0 0
Harvard University
Address [10] 0 0
Country [10] 0 0
Other collaborator category [11] 0 0
Other
Name [11] 0 0
Massachusetts General Hospital
Address [11] 0 0
Country [11] 0 0
Other collaborator category [12] 0 0
Other
Name [12] 0 0
Montreal Heart Institute
Address [12] 0 0
Country [12] 0 0
Other collaborator category [13] 0 0
Other
Name [13] 0 0
University of British Columbia
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Other
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University of Missouri, Kansas City
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Other
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Vanderbilt University
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Ethics approval
Ethics application status

Summary
Brief summary
The purpose of the ISCHEMIA trial is to determine the best management strategy for
higher-risk patients with stable ischemic heart disease (SIHD). This is a multicenter
randomized controlled trial with 5179 randomized participants with moderate or severe
ischemia on stress testing. A blinded coronary computed tomography angiogram (CCTA) was
performed in most participants with eGFR =60 mL/min/1.73m2 to identify and exclude
participants with either significant unprotected left main disease (=50% stenosis) or those
without obstructive CAD (<50% stenosis in all major coronary arteries). Of 8518 participants
enrolled, those that had insufficient ischemia, ineligible anatomy demonstrated on CCTA or
another exclusion criterion, did not go on to randomization. Eligible participants were then
assigned at random to a routine invasive strategy (INV) with cardiac catheterization followed
by revascularization, if feasible, plus optimal medical therapy (OMT) or to a conservative
strategy (CON) of OMT, with cardiac catheterization and revascularization reserved for those
who fail OMT.

SPECIFIC AIMS

A. Primary Aim The primary aim of the ISCHEMIA trial is to determine whether an initial
invasive strategy of cardiac catheterization followed by optimal revascularization, if
feasible, in addition to OMT, will reduce the primary composite endpoint of cardiovascular
death, nonfatal myocardial infarction, resuscitated cardiac arrest, or hospitalization for
unstable angina or heart failure in participants with SIHD and moderate or severe ischemia
over an average follow-up of approximately 3.5 years compared with an initial conservative
strategy of OMT alone with catheterization reserved for failure of OMT.

B. Secondary Aims Secondary aims are to determine whether an initial invasive strategy
compared to a conservative strategy will improve: 1) the composite of CV death or MI; 2)
angina symptoms and quality of life, as assessed by the Seattle Angina Questionnaire; 3)
all-cause mortality; 4) net clinical benefit assessed by including stroke in the primary and
secondary composite endpoints; and 5) individual components of the composite endpoints.

Condition: Coronary Disease Procedure: Coronary CT Angiogram Procedure: Cardiac
catheterization Phase: Phase III per NIH

Condition: Cardiovascular Diseases Procedure: Angioplasty, Transluminal, Percutaneous
Coronary, other catheter-based interventions Phase: Phase III per NIH

Condition: Heart Diseases Procedure: Coronary Artery Bypass Surgery Phase: Phase III per NIH
Trial website
https://clinicaltrials.gov/ct2/show/NCT01471522
Trial related presentations / publications
Maron DJ, Stone GW, Berman DS, Mancini GB, Scott TA, Byrne DW, Harrell FE Jr, Shaw LJ, Hachamovitch R, Boden WE, Weintraub WS, Spertus JA. Is cardiac catheterization necessary before initial management of patients with stable ischemic heart disease? Results from a Web-based survey of cardiologists. Am Heart J. 2011 Dec;162(6):1034-1043.e13. doi: 10.1016/j.ahj.2011.09.001.
Phillips LM, Hachamovitch R, Berman DS, Iskandrian AE, Min JK, Picard MH, Kwong RY, Friedrich MG, Scherrer-Crosbie M, Hayes SW, Sharir T, Gosselin G, Mazzanti M, Senior R, Beanlands R, Smanio P, Goyal A, Al-Mallah M, Reynolds H, Stone GW, Maron DJ, Shaw LJ. Lessons learned from MPI and physiologic testing in randomized trials of stable ischemic heart disease: COURAGE, BARI 2D, FAME, and ISCHEMIA. J Nucl Cardiol. 2013 Dec;20(6):969-75. doi: 10.1007/s12350-013-9773-4.
ISCHEMIA Trial Research Group; Maron DJ, Hochman JS, O'Brien SM, Reynolds HR, Boden WE, Stone GW, Bangalore S, Spertus JA, Mark DB, Alexander KP, Shaw L, Berger JS, Ferguson TB Jr, Williams DO, Harrington RA, Rosenberg Y. International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial: Rationale and design. Am Heart J. 2018 Jul;201:124-135. doi: 10.1016/j.ahj.2018.04.011. Epub 2018 Apr 21.
Hochman JS, Reynolds HR, Bangalore S, O'Brien SM, Alexander KP, Senior R, Boden WE, Stone GW, Goodman SG, Lopes RD, Lopez-Sendon J, White HD, Maggioni AP, Shaw LJ, Min JK, Picard MH, Berman DS, Chaitman BR, Mark DB, Spertus JA, Cyr DD, Bhargava B, Ruzyllo W, Wander GS, Chernyavskiy AM, Rosenberg YD, Maron DJ; ISCHEMIA Research Group. Baseline Characteristics and Risk Profiles of Participants in the ISCHEMIA Randomized Clinical Trial. JAMA Cardiol. 2019 Mar 1;4(3):273-286. doi: 10.1001/jamacardio.2019.0014. Erratum In: JAMA Cardiol. 2019 May 1;4(5):497.
Public notes

Contacts
Principal investigator
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Judith S Hochman, MD
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New York University
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