Cardiovascular DiseasesPhase 4ISCHEMIA-CKDNCT01985360
ISCHEMIA-Chronic Kidney Disease Trial
A Phase 4 study testing Cardiac Catheterization, Coronary Artery Bypass Graft Surgery and Percutaneous Coronary Intervention in people with Cardiovascular Diseases and Coronary Artery Disease, run by NYU Langone Health at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Cardiovascular Diseases, Coronary Artery Disease, Heart Diseases
- What is being tested?
- Cardiac Catheterization, Coronary Artery Bypass Graft Surgery and Percutaneous Coronary Intervention
- Type of treatment
- Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 777 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2014to Jul 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 27Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
NYU Langone Medical Center
New York, New York, 10016
About this study
Official title: 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 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
Read more
- 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).
- 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
Read the 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 studies in the CKD cohort suggest a long-term survival benefit of revascularization when compared with medical therapy alone, despite an 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 clinical equipoise in the management of these patients, with the rates of revascularization only around 10-45%. The results of ISCHEMIA-CKD will have profound implications for guidelines, health policy, and clinical practice.
- Conditions
- Cardiovascular Diseases, Coronary Artery Disease, Heart Diseases, Myocardial Ischemia, Kidney Disease, End Stage Renal Failure on Dialysis
- Being tested
- Cardiac Catheterization, Coronary Artery Bypass Graft Surgery, Percutaneous Coronary Intervention, Lifestyle, Medication
- Medical subject headings
- Cardiovascular Diseases, Coronary Artery Disease, Heart Diseases, Myocardial Ischemia, Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiac CatheterizationProcedure or surgery
Also called cath
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.
Coronary Artery Bypass Graft SurgeryProcedure or surgery
Also called CABG
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 InterventionProcedure or surgery
Also called PCI
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.
LifestyleBehavioural
Also called Behavior change
Diet, physical activity, smoking cessation
MedicationDrug
Also called Pharmacologic Therapy
antiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Behavioral: Lifestyle; Drug: Medication |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Death From Any Cause or Myocardial Infarction
Measured: 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).
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2013 (estimated)
- Study startJan 2014
- Primary completionJun 2019
- Study completionJul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 777 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- New York University, National Heart, Lung, and Blood Institute (NHLBI), Duke University, Stanford University, Columbia University
- Responsible party
- Sponsor
- Investigators
- Harmony Reynolds, MD, MHA, Principal investigator, NYU Langone HealthJudith Hochman, MD, Study chair, ISCHEMIA trial Chair, New York University School of MedicineDavid Maron, MD, Study chair, ISCHEMIA trial Co-chair, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01985360
- Sponsor's protocol ID
- 12-01059
- Other IDs
- U01HL117905
- Acronym
- ISCHEMIA-CKD
- Status last verified
- Sep 2021
- First submitted
- 4 Nov 2013
- Last updated
- 18 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 30172098Bangalore 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.
PubMed 24793673Bangalore 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.
PubMed 26547460Stone 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.
PubMed 26616030Bangalore 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.
PubMed 27692819Shroff 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.
PubMed 27493258Mathew 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.
PubMed 28040264Pandya 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.
PubMed 27863354Patel 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.
PubMed 28185167Bangalore 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.
PubMed 28487357Mathew 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.
PubMed 29571453Chaudhry 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.
PubMed 30078001Bangalore 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.
PubMed 26361150Bangalore 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.
PubMed 26297196Patel 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
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease Trial
- ClinicalTrials.gov ID
- NCT01985360
- Acronym / sponsor ID
- ISCHEMIA-CKD / 12-01059
- Conditions
- Cardiovascular Diseases, Coronary Artery Disease, Heart Diseases, Myocardial Ischemia, Kidney Disease, End Stage Renal Failure on Dialysis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 777 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- New York University, National Heart, Lung, and Blood Institute (NHLBI), Duke University, Stanford University, Columbia University
- Study start
- Jan 2014
- Primary completion
- Jun 2019 (actual)
- Study completion
- Jul 2020 (actual)
- First posted
- 15 Nov 2013 (estimated)
- Results
- Posted 10 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- 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).
- 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
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 studies in the CKD cohort suggest a long-term survival benefit of revascularization when compared with medical therapy alone, despite an 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 clinical equipoise in the management of these patients, with the rates of revascularization only around 10-45%. The results of ISCHEMIA-CKD will have profound implications for guidelines, health policy, and clinical practice.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Invasive Strategy (INV) | Active comparator | Procedure: Cardiac Catheterization, Procedure: Coronary Artery Bypass Graft Surgery, Procedure: Percutaneous Coronary Intervention, Behavioral: Lifestyle, Drug: MedicationRoutine invasive strategy with cardiac catheterization followed by revascularization (Percutaneous Coronary Intervention or Coronary Artery Bypass Graft Surgery) plus optimal medical therapy. |
| Conservative Strategy (CON) | Active comparator | Behavioral: Lifestyle, Drug: MedicationOptimal medical therapy with cardiac catheterization and revascularization reserved for patients with OMT failure. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (27 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cardiac CatheterizationAlso: cathNarrowed 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. | Procedure or surgery | Invasive Strategy (INV) |
| Coronary Artery Bypass Graft SurgeryAlso: CABGArtery 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. | Procedure or surgery | Invasive Strategy (INV) |
| Percutaneous Coronary InterventionAlso: PCIPercutaneous 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. | Procedure or surgery | Invasive Strategy (INV) |
| LifestyleAlso: Behavior changeDiet, physical activity, smoking cessation | Behavioural | Conservative Strategy (CON), Invasive Strategy (INV) |
| MedicationAlso: Pharmacologic Therapyantiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies | Drug | Conservative Strategy (CON), Invasive Strategy (INV) |
Primary outcome
Incidence of Death From Any Cause or Myocardial Infarction
Time frame: 2.2 years
Cumulative Event Rate of Death From Any Cause or Myocardial Infarction
Time frame: 3 years
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 30172098Bangalore 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.
- Background: PubMed 24793673Bangalore 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.
- Background: PubMed 26547460Bangalore 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.
- Background: PubMed 26616030Stone 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.
- Background: PubMed 27692819Bangalore 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.
- Background: PubMed 27493258Shroff 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.
- Background: PubMed 28040264Mathew 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.
- Background: PubMed 27863354Pandya 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.
- Background: PubMed 28185167Patel 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.
- Background: PubMed 28487357Bangalore 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.
- Background: PubMed 29571453Mathew 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.
- Background: PubMed 30078001Chaudhry 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.
- Official website of the ISCHEMIA TrialLink provided by the sponsor.
- Official website of the ISCHEMIA-CKD TrialLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Harmony Reynolds, MD, MHA principal investigator
NYU Langone Health
Judith Hochman, MD study chair
ISCHEMIA trial Chair, New York University School of Medicine
David Maron, MD study chair
ISCHEMIA trial Co-chair, Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Cardiac Catheterization, Coronary Artery Bypass Graft Surgery and Percutaneous Coronary Intervention in people with Cardiovascular Diseases and Coronary Artery Disease, run by NYU Langone Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Death From Any Cause or Myocardial Infarction (time frame: 2.2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01985360, which also lists 22 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2021.