International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA)

• Status: Active, not recruiting
• Trial end date: 2026-03-31
• Target enrollment: 0
• Participant gender: All

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

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: New York University School of Medicine; NYU Langone Health
• Collaborators: Albany Stratton VA Medical Center; Cedars-Sinai Medical Center; Columbia University; Duke University; East Carolina University; Emory University; Harvard University; Massachusetts General Hospital; Montreal Heart Institute; National Heart, Lung, and Blood Institute (NHLBI); New York University; Stanford University; University of British Columbia; University of Missouri, Kansas City; Vanderbilt University

Criteria

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

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)