The purpose of the ISCHEMIA-CKD trial is to determine the best management strategy for
patients with stable ischemic heart disease (SIHD), at least moderate inducible ischemia and
advanced chronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] <30
ml/min/1.73 m² or on dialysis). This is a multicenter randomized controlled trial of 777
randomized participants with advanced CKD. Participants were assigned at random to a routine
invasive strategy (INV) with cardiac catheterization (cath) followed by revascularization (if
suitable) plus optimal medical therapy (OMT) or to a conservative strategy (CON) of OMT, with
cath and revascularization reserved for those who fail OMT. The trial is designed to run
seamlessly in parallel to the main ISCHEMIA trial as a companion trial.
SPECIFIC AIMS
A. Primary Aim. The primary aim of the ISCHEMIA-CKD trial is to determine whether an invasive
strategy of cardiac cath followed by optimal revascularization, in addition to OMT, will
reduce the primary composite endpoint of death or nonfatal myocardial infarction in
participants with SIHD and advanced CKD over an average follow-up of approximately 2.8 years
compared with an initial conservative strategy of OMT alone with catheterization reserved for
those who fail OMT. The primary endpoint is time to centrally adjudicated death or nonfatal
myocardial infarction (MI).
B. Secondary Aims. Major: To compare the incident of the composite of death, nonfatal MI,
resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure, and
angina symptoms and quality of life, as assessed by the Seattle Angina Questionnaire, between
the INV and CON strategies. Other secondary aims include: comparing the incidence of the
composite of death, nonfatal MI, hospitalization for unstable angina, hospitalization for
heart failure, resuscitated cardiac arrest, or stroke; composite of death, nonfatal MI, or
stroke; composite endpoints incorporating cardiovascular death; composite endpoints
incorporating other definitions of MI as defined in the clinical event charter; individual
components of the primary and major secondary endpoints; stroke and health resource
utilization, costs, and cost effectiveness.
A major secondary aim of ISCHEMIA-CKD trial is to compare the quality of life (QOL)
outcomes-patients' symptoms, functioning and well-being-between those assigned to an invasive
strategy as compared with a conservative strategy. In the protocol, angina frequency and
disease-specific quality of life measured by the Seattle Angina Questionnaire (SAQ) Angina
Frequency and Quality of Life scales, respectively, are described as the tools that will be
used to make this comparative assessment. Recent work has indicated that it is possible to
combine the information from the individual domain scores in the SAQ into a new Summary Score
that captures the information from the SAQ Angina Frequency, Physical Limitation and Quality
of Life scales into a single overall score. The advantages of using a summary score as the
primary measure of QOL effects of a therapy are a single primary endpoint comparison rather
than two or three (eliminating concerns some may have about multiple comparisons) and a more
intuitive holistic (patient-centric) interpretation of the effectiveness results. With these
advantages in mind, the ISCHEMIA leadership has agreed that the SAQ Summary Score will be
designated as the primary way this secondary endpoint will be analyzed and interpreted, with
the individual SAQ scores being used in a secondary, explanatory and descriptive role. A key
subgroup analysis will be to stratify the results among those with daily/weekly angina
(baseline SAQ Angina Frequency score ≤60), monthly angina (SAQ Angina Frequency score 61-99)
and no angina (SAQ Angina Frequency score = 100).
Condition: Coronary Disease Procedure: Cardiac catheterization Phase: Phase III Condition:
Cardiovascular Diseases Procedure: Angioplasty, Transluminal, Percutaneous Coronary, other
catheter-based interventions Phase: Phase III Condition: Heart Diseases Procedure: Coronary
Artery Bypass Surgery Phase: Phase III
Phase:
Phase 4
Details
Lead Sponsor:
New York University School of Medicine NYU Langone Health
Collaborators:
Albany Stratton VA Medical Center Columbia University Duke University East Carolina University Harvard University National Heart, Lung, and Blood Institute (NHLBI) New York University Stanford University Vanderbilt University