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ISCHEMIA-Chronic Kidney Disease Trial

Overview

Información sobre este estudio

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 a target randomization of ~1000 patients with advanced CKD and at least moderate ischemia on stress testing. Participants will be assigned at random to a routine invasive strategy (INV) with cardiac catheterization (cath) followed by revascularization 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 ancillary trial. SPECIFIC AIMS A. Primary Aim. The primary aim of the ISCHEMIA-CKD trial is to determine whether an invasive strategy of routine early catheterization followed by optimal revascularization, in addition to OMT, will reduce the primary composite endpoint of death or nonfatal myocardial infarction in SIHD patients with advanced CKD and at least moderate ischemia over an average follow-up of approximately 4 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 angina-related quality of life between the INV and CON strategies. Other secondary aims include: comparing the incidence of the composite of cardiovascular death, nonfatal myocardial infarction, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure; composite of cardiovascular death or nonfatal myocardial infarction; cardiovascular death; non-fatal myocardial infarction; all-cause death; stroke; hospitalization for heart failure or unstable angina 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

Elegibilidad para la participación

Los requisitos de elegibilidad de los participantes incluyen la edad, el sexo, el tipo y el estadio de la enfermedad, y los problemas de salud o tratamientos previos. Las pautas difieren de un estudio a otro e identifican quiénes pueden o no pueden participar. No hay garantía de que cada persona elegible que desee participar en un ensayo se inscribirá. Comunícate con el equipo del estudio para analizar la elegibilidad del estudio y la posible participación.

Inclusion Criteria:

  • At least moderate ischemia on a stress imaging test with nuclear myocardial perfusion (≥10% myocardium), echo or cardiac magnetic resonance wall motion (≥3/16 segments with stress-induced severe hypokinesis or akinesis).
  • Participant is willing to comply with all aspects of the protocol, including adherence to the assigned strategy, medical therapy and follow-up visits
  • Participant is willing to give written informed consent
  • Age ≥ 21 years
  • Advanced CKD (eGFR <30 or on dialysis)

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 CAD" (<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 graft surgery (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
  • New York Heart Association 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 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 (known to be pregnant; to be confirmed before randomization, if applicable)
  • Patient who, in the judgment of the patient's physician, is likely to have significant unprotected left main stenosis
  • Enrolled in a competing trial that involves a non-approved cardiac drug or device
  • Inability to comply with the protocol
  • Exceeds the weight or size limit for cardiac catheterization at the site
  • 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 at any time, unless coronary anatomy has been demonstrated within the previous 12 months to be suitable for PCI or CABG to accomplish complete revascularization of ischemic areas.

Sedes participantes de Mayo Clinic

Los estatus de los estudios cambian con frecuencia. Comunícate con el equipo del estudio para obtener la información más actualizada acerca de la posibilidad de participar.

Sede de Mayo Clinic Estatus

Rochester, Minn.

Investigador principal de Mayo Clinic

Patricia Pellikka, M.D.

Cerrado para la inscripción

More information

Publicaciones

  • Patients with chronic kidney disease (CKD) and stable ischemic heart disease are at markedly increased risk of cardiovascular events. Prior trials comparing a strategy of optimal medical therapy (OMT) with or without revascularization have largely excluded patients with advanced CKD. Whether a routine invasive approach when compared with a conservative strategy is beneficial in such patients is unknown. Read More on PubMed
  • Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality among patients with chronic kidney disease (CKD) with a glomerular filtration rate of < 60 mL/min/1.73 m2 body surface area. The availability of high-quality randomized controlled trial data to guide management for the population with CKD and ASCVD is limited. Understanding current practice patterns among providers caring for individuals with CKD and CVD is important in guiding future trial questions. Read More on PubMed
  • Patients with chronic kidney disease (CKD) have a high prevalence of atherosclerotic cardiovascular disease, likely reflecting the presence of traditional risk factors. A greater distinguishing feature of atherosclerotic cardiovascular disease in CKD is the severity of the disease, which is reflective of an increase in inflammatory mediators and vascular calcification secondary to hyperparathyroidism of renal origin that are unique to patients with CKD. Additional components of atherosclerotic cardiovascular disease that are prominent in patients with CKD include microvascular disease and myocardial fibrosis. Therapeutic interventions that minimize cardiovascular events related to atherosclerotic cardiovascular disease in patients with CKD, as determined by well-designed clinical trials, are limited to statins. Data are lacking regarding other available therapeutic measures primarily due to exclusion of patients with CKD from major trials studying cardiovascular disease. Data from well-designed randomized controlled trials are needed to guide clinicians who care for this high-risk population in the management of atherosclerotic cardiovascular disease to improve clinical outcomes. Read More on PubMed
  • Stable ischemic heart disease (SIHD) is a highly prevalent condition associated with increased costs, morbidity, and mortality. Management goals of SIHD can broadly be thought of in terms of improving prognosis and/or improving symptoms. Treatment options include medical therapy as well as revascularization, either with percutaneous coronary intervention or coronary artery bypass grafting. Herein, we will review the current evidence base for treatment of SIHD as well as its challenges and discuss ongoing studies to help address some of these knowledge gaps. Read More on PubMed
  • Patients with chronic kidney disease (CKD) undergoing coronary angiography (CA), adequate hydration and minimizing volume of contrast media (CM) are class 1b recommendations for preventing contrast induced nephropathy (CIN). Current data are insufficient to justify specific recommendations about isoosmolar vs. low-osmolar contrast media by the ACCF/AHA/SCAI guidelines. Read More on PubMed
  • Coronary revascularization decisions for patients with CKD stage 5D present a dilemma for clinicians because of high baseline risks of mortality and future cardiovascular events. This population differs from the general population regarding characteristics of coronary plaque composition and behavior, accuracy of noninvasive testing, and response to surgical and percutaneous revascularization, such that findings from the general population cannot be automatically extrapolated. However, this high-risk population has been excluded from all randomized trials evaluating outcomes of revascularization. Observational studies have attempted to address long-term outcomes after surgical versus percutaneous revascularization strategies, but inherent selection bias may limit accuracy. Compared with percutaneous strategies, surgical revascularization seems to have long-term survival benefit on the basis of observational data but associates with substantially higher short-term mortality rates. Percutaneous revascularization with drug-eluting and bare metal stents associates with a high risk of in-stent restenosis and need for future revascularization, perhaps contributing to the higher long-term mortality hazard. Off-pump coronary bypass surgery and the newest generation of drug-eluting stent platforms offer no definitive benefits. In this review, we address the nuances, complexities, and tradeoffs that clinicians face in determining the optimal method of coronary revascularization for this high-risk population. Read More on PubMed
  • All patients with stable ischemic heart disease (SIHD) should be managed with guideline-directed medical therapy (GDMT), which reduces progression of atherosclerosis and prevents coronary thrombosis. Revascularization is also indicated in patients with SIHD and progressive or refractory symptoms, despite medical management. Whether a strategy of routine revascularization (with percutaneous coronary intervention or coronary artery bypass graft surgery as appropriate) plus GDMT reduces rates of death or myocardial infarction, or improves quality of life compared to an initial approach of GDMT alone in patients with substantial ischemia is uncertain. Opinions run strongly on both sides, and evidence may be used to support either approach. Careful review of the data demonstrates the limitations of our current knowledge, resulting in a state of community equipoise. The ongoing ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) is being performed to determine the optimal approach to managing patients with SIHD, moderate-to-severe ischemia, and symptoms that can be controlled medically. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522). Read More on PubMed
  • Randomized trials of percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) routinely exclude patients with chronic kidney disease (CKD). Read More on PubMed
  • A recent study has shown an association between high-potency statins and risk of acute kidney injury. However, these data are from observational studies, and it is not clear if similar signal is seen from randomized controlled trials. We evaluated the risk of renal-associated serious adverse events (SAEs) using statins versus placebo trials and the high-dose versus low-dose statin trials that were available to us. The outcome of interest was renal-related SAEs. The incidence of adverse events relating to kidney injury was determined through review of the adverse event database. The following outcomes were evaluated: (1) renal-related SAEs within 120 days of randomization (primary outcome), (2) renal-related SAEs after 120 days of randomization (secondary), and (3) drug discontinuation due to renal-related SAEs (secondary). There was no difference in the incidence of renal-related SAEs at 120 days (0.04% vs 0.10%, p = 0.162) between atorvastatin and placebo in the 24 placebo-controlled trials (10,345 patients on atorvastatin (10 to 80 mg/day) versus 8,945 patients on placebo) or in the high-dose versus low-dose statin trials including the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study (0.05% vs 0.02%, p = 0.625) or the Treating to New Targets (TNT) trial (0.0% vs 0.04%, p = 0.500) trial. Results were similar for renal-related SAEs after 120 days (placebo controlled trials [0.38% vs 0.36%, p = 0.905], IDEAL trial [0.56% vs 0.65%, p = 0.683], or the TNT trial [0.76% vs 1.04%, p = 0.168]) and for drug withdrawal due to renal-related SAE (placebo controlled trials [0.05% vs 0.04%, p = 1.00], IDEAL trial [0.02% vs 0.0%, p = 0.499], or the TNT trial [0.08% vs 0.12%, p = 0.754]). In conclusion, the results from clinical trials with data from 149,882 patient-years of follow-up fail to show any increase in renal-related SAEs with statins compared with controls. Read More on PubMed

Otros temas en investigación

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CLS-20303080

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