ISCHEMIA-Chronic Kidney Disease Trial

NCT01985360 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: 12-01059U01HL117905
• Study Type: interventional
• Target: 777
• Locations: 1 country
• Sites: 1

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 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

Conditions

Cardiovascular Diseases; Coronary Artery Disease; Heart Diseases; Myocardial Ischemia; Kidney Disease; End Stage Renal Failure on Dialysis

Outcome Measures

Primary Outcomes (2)

• Incidence of Death From Any Cause or Myocardial Infarction

  2.2 years

• Cumulative Event Rate of Death From Any Cause or Myocardial Infarction

  This measure represents the estimated cumulative probability of experiencing Death from any cause or Myocardial Infarction within the indicated timeframe in each treatment group. The interpretation of the measure is similar to Kaplan-Meier event rates. Estimates are expressed as percentages ranging from 0% (endpoint is certain not to occur) to 100% (endpoint is certain to occur).

  3 years

Study Arms (2)

Invasive Strategy (INV)

ACTIVE COMPARATOR

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; Procedure: Coronary Artery Bypass Graft Surgery; Procedure: Percutaneous Coronary Intervention; Behavioral: Lifestyle; Drug: Medication

Conservative Strategy (CON)

ACTIVE COMPARATOR

Optimal medical therapy with cardiac catheterization and revascularization reserved for patients with OMT failure.

Behavioral: Lifestyle; Drug: Medication

Interventions

Cardiac Catheterization PROCEDURE

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.

Also known as: cath

Invasive Strategy (INV)

Coronary Artery Bypass Graft Surgery PROCEDURE

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.

Also known as: CABG

Invasive Strategy (INV)

Percutaneous Coronary Intervention PROCEDURE

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.

Also known as: PCI

Invasive Strategy (INV)

Lifestyle BEHAVIORAL

Diet, physical activity, smoking cessation

Also known as: Behavior change

Conservative Strategy (CON); Invasive Strategy (INV)

Medication DRUG

antiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies

Also known as: Pharmacologic Therapy

Conservative Strategy (CON); Invasive Strategy (INV)

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• NYU Langone Health: lead
• New York University: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Duke University: collaborator
• Stanford University: collaborator
• Columbia University: collaborator

Study Sites (1)

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Related Publications (22)

• Bangalore S, Maron DJ, Fleg JL, O'Brien SM, Herzog CA, Stone GW, Mark DB, Spertus JA, Alexander KP, Sidhu MS, Chertow GM, Boden WE, Hochman JS; ISCHEMIA-CKD Research Group. International Study of Comparative Health Effectiveness with Medical and Invasive Approaches-Chronic Kidney Disease (ISCHEMIA-CKD): Rationale and design. Am Heart J. 2018 Nov;205:42-52. doi: 10.1016/j.ahj.2018.07.023. Epub 2018 Aug 1.

  PMID: 30172098 BACKGROUND

• Bangalore S, Fayyad R, Hovingh GK, Laskey R, Vogt L, DeMicco DA, Waters DD; Treating to New Targets Steering Committee and Investigators. Statin and the risk of renal-related serious adverse events: Analysis from the IDEAL, TNT, CARDS, ASPEN, SPARCL, and other placebo-controlled trials. Am J Cardiol. 2014 Jun 15;113(12):2018-20. doi: 10.1016/j.amjcard.2014.03.046. Epub 2014 Apr 3.

  PMID: 24793673 BACKGROUND

• Bangalore S, Maron DJ, Hochman JS. Evidence-Based Management of Stable Ischemic Heart Disease: Challenges and Confusion. JAMA. 2015 Nov 10;314(18):1917-8. doi: 10.1001/jama.2015.11219. No abstract available.

  PMID: 26547460 BACKGROUND

• Stone GW, Hochman JS, Williams DO, Boden WE, Ferguson TB Jr, Harrington RA, Maron DJ. Medical Therapy With Versus Without Revascularization in Stable Patients With Moderate and Severe Ischemia: The Case for Community Equipoise. J Am Coll Cardiol. 2016 Jan 5;67(1):81-99. doi: 10.1016/j.jacc.2015.09.056. Epub 2015 Nov 23.

  PMID: 26616030 BACKGROUND

• Bangalore S. Diagnostic, Therapeutic, and Clinical Trial Conundrum of Patients With Chronic Kidney Disease. JACC Cardiovasc Interv. 2016 Oct 24;9(20):2110-2112. doi: 10.1016/j.jcin.2016.08.031. Epub 2016 Sep 28. No abstract available.

  PMID: 27692819 BACKGROUND

• Shroff GR, Herzog CA. Coronary Revascularization in Patients with CKD Stage 5D: Pragmatic Considerations. J Am Soc Nephrol. 2016 Dec;27(12):3521-3529. doi: 10.1681/ASN.2016030345. Epub 2016 Aug 4.

  PMID: 27493258 BACKGROUND

• Mathew RO, Bangalore S, Lavelle MP, Pellikka PA, Sidhu MS, Boden WE, Asif A. Diagnosis and management of atherosclerotic cardiovascular disease in chronic kidney disease: a review. Kidney Int. 2017 Apr;91(4):797-807. doi: 10.1016/j.kint.2016.09.049. Epub 2016 Dec 28.

  PMID: 28040264 BACKGROUND

• Pandya B, Chalhoub JM, Parikh V, Gaddam S, Spagnola J, El-Sayegh S, Bogin M, Kandov R, Lafferty J, Bangalore S. Contrast media use in patients with chronic kidney disease undergoing coronary angiography: A systematic review and meta-analysis of randomized trials. Int J Cardiol. 2017 Feb 1;228:137-144. doi: 10.1016/j.ijcard.2016.11.170. Epub 2016 Nov 9.

  PMID: 27863354 BACKGROUND

• Patel AV, Bangalore S. Challenges with Evidence-Based Management of Stable Ischemic Heart Disease. Curr Cardiol Rep. 2017 Feb;19(2):11. doi: 10.1007/s11886-017-0820-7.

  PMID: 28185167 BACKGROUND

• Bangalore S, Briguori C. Preventive Strategies for Contrast-Induced Acute Kidney Injury: And the Winner Is.... Circ Cardiovasc Interv. 2017 May;10(5):e005262. doi: 10.1161/CIRCINTERVENTIONS.117.005262. No abstract available.

  PMID: 28487357 BACKGROUND

• Mathew RO, Bangalore S, Sidhu MS, Fleg JL, Maddux FW. Increasing inclusion of patients with advanced chronic kidney disease in cardiovascular clinical trials. Kidney Int. 2018 Apr;93(4):787-788. doi: 10.1016/j.kint.2017.11.028. No abstract available.

  PMID: 29571453 BACKGROUND

• Chaudhry RI, Mathew RO, Sidhu MS, Sidhu-Adler P, Lyubarova R, Rangaswami J, Salman L, Asif A, Fleg JL, McCullough PA, Maddux F, Bangalore S. Detection of Atherosclerotic Cardiovascular Disease in Patients with Advanced Chronic Kidney Disease in the Cardiology and Nephrology Communities. Cardiorenal Med. 2018;8(4):285-295. doi: 10.1159/000490768. Epub 2018 Aug 3.

  PMID: 30078001 BACKGROUND

• Bangalore S, Guo Y, Samadashvili Z, Blecker S, Xu J, Hannan EL. Revascularization in Patients With Multivessel Coronary Artery Disease and Chronic Kidney Disease: Everolimus-Eluting Stents Versus Coronary Artery Bypass Graft Surgery. J Am Coll Cardiol. 2015 Sep 15;66(11):1209-1220. doi: 10.1016/j.jacc.2015.06.1334.

  PMID: 26361150 BACKGROUND

• Bangalore S. Stress testing in patients with chronic kidney disease: The need for ancillary markers for effective risk stratification and prognosis. J Nucl Cardiol. 2016 Jun;23(3):570-4. doi: 10.1007/s12350-015-0264-7. Epub 2015 Aug 22. No abstract available.

  PMID: 26297196 BACKGROUND

• Patel A, Bangalore S. Revascularization Strategies in Chronic Kidney Disease: Percutaneous Coronary Intervention vs. Coronary Artery Bypass Graft Surgery. Janani Rangaswami, Dr. Edgar V. Lerman, and Dr. Claudio Ronco (Eds), Cardio-nephrology: Confluence of the Heart and Kidney in Clinical Practice. London: Springer-Verlag

  BACKGROUND

• Sidhu MS, Alexander KP, Huang Z, Mathew RO, Newman JD, O'Brien SM, Pellikka PA, Lyubarova R, Bockeria O, Briguori C, Kretov EL, Mazurek T, Orso F, Roik MF, Sajeev C, Shutov EV, Rockhold FW, Borrego D, Balter S, Stone GW, Chaitman BR, Goodman SG, Fleg JL, Reynolds HR, Maron DJ, Hochman JS, Bangalore S; ISCHEMIA-CKD Research Group. Cause-Specific Mortality in Patients With Advanced Chronic Kidney Disease in the ISCHEMIA-CKD Trial. JACC Cardiovasc Interv. 2023 Jan 23;16(2):209-218. doi: 10.1016/j.jcin.2022.10.062.

  PMID: 36697158 DERIVED

• Mathew RO, Maron DJ, Anthopolos R, Fleg JL, O'Brien SM, Rockhold FW, Briguori C, Roik MF, Mazurek T, Demkow M, Malecki R, Ye Z, Kaul U, Miglinas M, Stone GW, Wald R, Charytan DM, Sidhu MS, Hochman JS, Bangalore S. Guideline-Directed Medical Therapy Attainment and Outcomes in Dialysis-Requiring Versus Nondialysis Chronic Kidney Disease in the ISCHEMIA-CKD Trial. Circ Cardiovasc Qual Outcomes. 2022 Oct;15(10):e008995. doi: 10.1161/CIRCOUTCOMES.122.008995. Epub 2022 Oct 4.

  PMID: 36193750 DERIVED

• Chaitman BR, Cyr DD, Alexander KP, Pracon R, Bainey KR, Mathew A, Acharya A, Kunichoff DF, Fleg JL, Lopes RD, Sidhu MS, Anthopolos R, Rockhold FW, Stone GW, Maron DJ, Hochman JS, Bangalore S. Cardiovascular and Renal Implications of Myocardial Infarction in the ISCHEMIA-CKD Trial. Circ Cardiovasc Interv. 2022 Aug;15(8):e012103. doi: 10.1161/CIRCINTERVENTIONS.122.012103. Epub 2022 Aug 16.

  PMID: 35973009 DERIVED

• Briguori C, Mathew RO, Huang Z, Mavromatis K, Hickson LJ, Lau WL, Mathew A, Mahajan S, Wheeler DC, Claes KJ, Chen G, Nolasco FEB, Stone GW, Fleg JL, Sidhu MS, Rockhold FW, Chertow GM, Hochman JS, Maron DJ, Bangalore S. Dialysis Initiation in Patients With Chronic Coronary Disease and Advanced Chronic Kidney Disease in ISCHEMIA-CKD. J Am Heart Assoc. 2022 Mar 15;11(6):e022003. doi: 10.1161/JAHA.121.022003. Epub 2022 Mar 9.

  PMID: 35261290 DERIVED

• Herzog CA, Simegn MA, Xu Y, Costa SP, Mathew RO, El-Hajjar MC, Gulati S, Maldonado RA, Daugas E, Madero M, Fleg JL, Anthopolos R, Stone GW, Sidhu MS, Maron DJ, Hochman JS, Bangalore S. Kidney Transplant List Status and Outcomes in the ISCHEMIA-CKD Trial. J Am Coll Cardiol. 2021 Jul 27;78(4):348-361. doi: 10.1016/j.jacc.2021.05.001. Epub 2021 May 11.

  PMID: 33989711 DERIVED

• Bangalore S, Maron DJ, O'Brien SM, Fleg JL, Kretov EI, Briguori C, Kaul U, Reynolds HR, Mazurek T, Sidhu MS, Berger JS, Mathew RO, Bockeria O, Broderick S, Pracon R, Herzog CA, Huang Z, Stone GW, Boden WE, Newman JD, Ali ZA, Mark DB, Spertus JA, Alexander KP, Chaitman BR, Chertow GM, Hochman JS; ISCHEMIA-CKD Research Group. Management of Coronary Disease in Patients with Advanced Kidney Disease. N Engl J Med. 2020 Apr 23;382(17):1608-1618. doi: 10.1056/NEJMoa1915925. Epub 2020 Mar 30.

  PMID: 32227756 DERIVED

• Spertus JA, Jones PG, Maron DJ, Mark DB, O'Brien SM, Fleg JL, Reynolds HR, Stone GW, Sidhu MS, Chaitman BR, Chertow GM, Hochman JS, Bangalore S; ISCHEMIA-CKD Research Group. Health Status after Invasive or Conservative Care in Coronary and Advanced Kidney Disease. N Engl J Med. 2020 Apr 23;382(17):1619-1628. doi: 10.1056/NEJMoa1916374. Epub 2020 Mar 30.

  PMID: 32227754 DERIVED

Related Links

• Official website of the ISCHEMIA Trial
• Official website of the ISCHEMIA-CKD Trial

MeSH Terms

Conditions

Cardiovascular Diseases; Coronary Artery Disease; Heart Diseases; Myocardial Ischemia; Kidney Diseases

Interventions

Cardiac Catheterization; Coronary Artery Bypass; Percutaneous Coronary Intervention; Dosage Forms; Drug Therapy

Condition Hierarchy (Ancestors)

Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Catheterization; Therapeutics; Investigative Techniques; Myocardial Revascularization; Cardiac Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Vascular Grafting; Vascular Surgical Procedures; Thoracic Surgical Procedures; Endovascular Procedures; Minimally Invasive Surgical Procedures; Pharmaceutical Preparations; Technology, Pharmaceutical

Results Point of Contact

• Title: Sripal Bangalore
• Organization: NYU Langone Health

Sripal.Bangalore@nyulangone.org

(212) 263 3540

Study Officials

• Harmony Reynolds, MD, MHA

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

• Judith Hochman, MD

  ISCHEMIA trial Chair, New York University School of Medicine

  STUDY CHAIR

• David Maron, MD

  ISCHEMIA trial Co-chair, Stanford University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2013
• First Posted: November 15, 2013
• Study Start: January 1, 2014
• Primary Completion: June 1, 2019
• Study Completion: July 1, 2020
• Last Updated: October 18, 2021
• Results First Posted: September 10, 2020

Record last verified: 2021-09

Locations

US (1)