ISCHEMIA-Chronic Kidney Disease Trial
Condition: Cardiovascular Diseases; Coronary Artery Disease; Heart Diseases; Myocardial Ischemia; Kidney Disease; End Stage Renal Failure on Dialysis
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Cardiovascular Diseases; Coronary Artery Disease; Myocardial Ischemia; Heart Diseases; Ischemia
Intervention: Cardiac Catheterization; Coronary Artery Bypass Graft Surgery; Percutaneous Coronary Intervention; Lifestyle; Medication
Intervention description: 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.; 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.; 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.; Diet, physical activity, smoking cessation; antiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 777.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility criteria:

        Inclusion Criteria:

          -  At least moderate ischemia on an exercise or pharmacologic stress test

          -  End-stage renal disease on dialysis or estimated glomerular filtration rate (eGFR)
             <30mL/min/1.73m²

          -  Willingness to comply with all aspects of the protocol, including adherence to the
             assigned strategy, medical therapy and follow-up visits

          -  Willingness to give written informed consent

          -  Age ≥ 21 years

        Exclusion Criteria:

          -  Left Ventricular Ejection Fraction < 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 coronary artery disease" (<50% stenosis in all major
             epicardial vessels) on prior CCTA or prior catheterization, performed within 12 months

          -  Coronary anatomy unsuitable for either percutaneous coronary intervention (PCI) or
             coronary artery bypass grafting (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

          -  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

          -  High likelihood of significant unprotected left main stenosis, in the judgment of the
             patient's physician

          -  Enrollment in a competing trial that involves a non-approved cardiac drug or device

          -  Inability to comply with the protocol

          -  Body weight or size exceeding the limit for 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