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ISCHEMIA-Chronic Kidney Disease Trial (ISCHEMIA-CKD)

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ClinicalTrials.gov Identifier: NCT01985360
Recruitment Status : Active, not recruiting
First Posted : November 15, 2013
Last Update Posted : September 14, 2018
Sponsor:
Collaborators:
New York University
National Heart, Lung, and Blood Institute (NHLBI)
Duke University
Stanford University
Columbia University
Information provided by (Responsible Party):
New York University School of Medicine

November 4, 2013
November 15, 2013
September 14, 2018
January 2014
June 2019   (Final data collection date for primary outcome measure)
Time to first occurrence of death or nonfatal MI. [ Time Frame: ~2.8 year follow-up ]
Time to first occurrence of death or nonfatal myocardial infarction. [ Time Frame: ~four year follow-up ]
Complete list of historical versions of study NCT01985360 on ClinicalTrials.gov Archive Site
  • Composite of death, nonfatal MI, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure [ Time Frame: ~four year follow-up ]
  • Angina control per SAQ Angina Frequency Scale [ Time Frame: ~four year follow-up ]
  • Disease specific quality of life per SAQ Quality of Life Scale [ Time Frame: ~four year follow-up ]
  • Composite of death, nonfatal MI, hospitalization for unstable angina, hospitalization for heart failure, resuscitated cardiac arrest, or stroke [ Time Frame: ~four year follow-up ]
  • Composite of death, nonfatal MI, or stroke [ Time Frame: ~four year follow-up ]
  • Composite endpoints incorporating cardiovascular death [ Time Frame: ~four year follow-up ]
  • Composite endpoints incorporating other definitions of MI as defined in the clinical event charter [ Time Frame: ~four year follow-up ]
  • Individual components of the primary and major secondary endpoints [ Time Frame: ~four year follow-up ]
  • Stroke [ Time Frame: ~four year follow-up ]
  • Health resource utilization, costs, and cost effectiveness [ Time Frame: ~four year follow-up ]
  • Angina control per Seattle Angina Questionnaire (SAQ) Angina Frequency Scale [ Time Frame: ~four year follow-up ]
  • Composite of cardiovascular death, nonfatal myocardial infarction, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure [ Time Frame: ~four year follow-up ]
  • Death [ Time Frame: ~four year follow-up ]
  • Cardiovascular death [ Time Frame: ~four year follow-up ]
  • Myocardial Infarction [ Time Frame: ~four year follow-up ]
  • Resuscitated cardiac arrest [ Time Frame: ~four year follow-up ]
  • Hospitalization for unstable angina [ Time Frame: ~four year follow-up ]
  • Hospitalization for heart failure [ Time Frame: ~four year follow-up ]
  • Stroke [ Time Frame: ~four year follow-up ]
  • Cardiovascular death or non-fatal myocardial infarction [ Time Frame: ~four year follow-up ]
Not Provided
Not Provided
 
ISCHEMIA-Chronic Kidney Disease Trial
International Study of Comparative Health Effectiveness With Medical and Invasive Approaches—Chronic Kidney Disease Trial

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 ischemia and advanced chronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] <30 or on dialysis). This is a multicenter randomized controlled trial with 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 catheterization 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; angina control per SAQ Angina Frequency Scale; disease specific quality of life per SAQ Quality of Life Scale 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.

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

BACKGROUND:

Among patients with advanced CKD, cardiovascular disease is the leading cause of death,15-30 times higher than the age-adjusted cardiovascular mortality rate in the general population. The projected 4-year mortality is >50% in patients with advanced CKD and is worse than that for patients in the general population who have cancers, heart failure, stroke or MI. Participants with advanced CKD are 5-10 times more likely to die than to reach end stage renal disease (ESRD). Despite this, ~80% of contemporary coronary artery disease (CAD) trials exclude participants with advanced CKD. Most of the treatments aimed at reducing cardiovascular events in advanced CKD are therefore extrapolated from cohorts without advanced CKD. Participants with advanced CKD and cardiovascular disease are undertreated with less frequent use of statins and revascularization therapies, and the optimal management approach to these patients is unknown. Participants with advanced CKD are notably underrepresented in contemporary trials comparing revascularization with medical therapy in SIHD patients, such as the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial or the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial,making any assessment about the efficacy of revascularization plus medical therapy vs. initial medical therapy alone in this cohort problematic.

Participants with advanced CKD are at increased risk for complications of the assigned invasive procedure, specifically contrast-induced acute kidney injury (AKI), dialysis, major bleeding and short-term risk of death. However, there is controversy in the medical literature regarding the incidence (<1% to >30%), effective treatment (saline hydration, N-acetyl cysteine, or sodium bicarbonate) and prognosis of contrast induced AKI (<0.5% to >5% requiring dialysis). In addition although contrast induced AKI have been associated with increase in short-term mortality residual confounding in these studies makes interpretation difficulty. Moreover it is unknown if these short-term increased risks are offset by long-term benefits. Limited observational study in the CKD cohort suggests a survival benefit of revascularization when compared with medical therapy alone long-term, despite increase in short-term risks. However, the medical therapy in these trials was not optimized, drug eluting stents were rarely used and there is undoubtedly inherent selection and ascertainment bias with observational studies. The above has resulted in substantial clinical equipoise in the management of these patients with the rates of revascularization of only around 10-45%. The results of ISCHEMIA-CKD will have profound implications for guidelines, health policy, and clinical practice.

Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Cardiovascular Diseases
  • Coronary Artery Disease
  • Heart Diseases
  • Myocardial Ischemia
  • Kidney Disease
  • End Stage Renal Failure on Dialysis
  • Procedure: 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.
    Other Name: cath
  • Procedure: 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.
    Other Name: CABG
  • Procedure: 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.
    Other Name: PCI
  • Behavioral: Lifestyle
    Diet, physical activity, smoking cessation
    Other Name: Behavior change
  • Drug: Medication
    antiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies
    Other Name: Pharmacologic Therapy
  • Active Comparator: Invasive Strategy (INV)
    Routine invasive strategy with cardiac catheterization followed by revascularization (Percutaneous Coronary Intervention or Coronary Artery Bypass Graft Surgery) plus optimal medical therapy.
    Interventions:
    • Procedure: Cardiac Catheterization
    • Procedure: Coronary Artery Bypass Graft Surgery
    • Procedure: Percutaneous Coronary Intervention
    • Behavioral: Lifestyle
    • Drug: Medication
  • Active Comparator: Conservative Strategy (CON)
    Optimal medical therapy with cardiac catheterization and revascularization reserved for patients with OMT failure.
    Interventions:
    • Behavioral: Lifestyle
    • Drug: Medication
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
777
1000
December 2019
June 2019   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
21 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01985360
12-01059
U01HL117905 ( U.S. NIH Grant/Contract )
Yes
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Not Provided
New York University School of Medicine
New York University School of Medicine
  • New York University
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Duke University
  • Stanford University
  • Columbia University
Principal Investigator: Sripal Bangalore, MD, MHA New York University School of Medicine
Study Chair: Judith Hochman, MD ISCHEMIA trial Chair, New York University School of Medicine
Study Chair: David Maron, MD ISCHEMIA trial Co-chair, Stanford University
New York University School of Medicine
September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP