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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 : April 25, 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

Brief 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 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


Condition or disease Intervention/treatment Phase
Cardiovascular Diseases Coronary Artery Disease Heart Diseases Myocardial Ischemia Kidney Disease End Stage Renal Failure on Dialysis Procedure: Cardiac Catheterization Procedure: Coronary Artery Bypass Graft Surgery Procedure: Percutaneous Coronary Intervention Behavioral: Lifestyle Drug: Medication Phase 4

Detailed Description:

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 777 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: International Study of Comparative Health Effectiveness With Medical and Invasive Approaches—Chronic Kidney Disease Trial
Study Start Date : January 2014
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases
U.S. FDA Resources

Arm Intervention/treatment
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.
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: Conservative Strategy (CON)
Optimal medical therapy with cardiac catheterization and revascularization reserved for patients with OMT failure.
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



Primary Outcome Measures :
  1. Time to first occurrence of death or nonfatal MI. [ Time Frame: ~2.8 year follow-up ]

Secondary Outcome Measures :
  1. Composite of death, nonfatal MI, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure [ Time Frame: ~four year follow-up ]
  2. Angina control per SAQ Angina Frequency Scale [ Time Frame: ~four year follow-up ]
  3. Disease specific quality of life per SAQ Quality of Life Scale [ Time Frame: ~four year follow-up ]
  4. Composite of death, nonfatal MI, hospitalization for unstable angina, hospitalization for heart failure, resuscitated cardiac arrest, or stroke [ Time Frame: ~four year follow-up ]
  5. Composite of death, nonfatal MI, or stroke [ Time Frame: ~four year follow-up ]
  6. Composite endpoints incorporating cardiovascular death [ Time Frame: ~four year follow-up ]
  7. Composite endpoints incorporating other definitions of MI as defined in the clinical event charter [ Time Frame: ~four year follow-up ]
  8. Individual components of the primary and major secondary endpoints [ Time Frame: ~four year follow-up ]
  9. Stroke [ Time Frame: ~four year follow-up ]
  10. Health resource utilization, costs, and cost effectiveness [ Time Frame: ~four year follow-up ]


Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01985360


Locations
United States, New York
NYU Langone Medical Center
New York, New York, United States, 10016
Sponsors and Collaborators
New York University School of Medicine
New York University
National Heart, Lung, and Blood Institute (NHLBI)
Duke University
Stanford University
Columbia University
Investigators
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

Additional Information:
Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT01985360     History of Changes
Other Study ID Numbers: 12-01059
U01HL117905 ( U.S. NIH Grant/Contract )
First Posted: November 15, 2013    Key Record Dates
Last Update Posted: April 25, 2018
Last Verified: April 2018

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

Additional relevant MeSH terms:
Cardiovascular Diseases
Kidney Diseases
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Renal Insufficiency, Chronic
Ischemia
Renal Insufficiency
Kidney Failure, Chronic
Urologic Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes