ISCHEMIA-Chronic Kidney Disease Trial
关键词
抽象
描述
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.
日期
| 最后验证: | 08/31/2020 |
| 首次提交: | 11/03/2013 |
| 提交的预估入学人数: | 11/13/2013 |
| 首次发布: | 11/14/2013 |
| 上次提交的更新: | 09/07/2020 |
| 最近更新发布: | 09/09/2020 |
| 首次提交结果的日期: | 06/30/2020 |
| 首次提交质量检查结果的日期: | 09/07/2020 |
| 首次发布结果的日期: | 09/09/2020 |
| 实际学习开始日期: | 12/31/2013 |
| 预计主要完成日期: | 05/31/2019 |
| 预计完成日期: | 06/30/2020 |
状况或疾病
干预/治疗
Procedure: Invasive Strategy (INV)
Procedure: Invasive Strategy (INV)
Procedure: Invasive Strategy (INV)
Behavioral: Lifestyle
Drug: Medication
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| 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: Invasive Strategy (INV) 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. |
| Active Comparator: Conservative Strategy (CON) Optimal medical therapy with cardiac catheterization and revascularization reserved for patients with OMT failure. |
资格标准
| 有资格学习的年龄 | 21 Years 至 21 Years |
| 有资格学习的性别 | All |
| 接受健康志愿者 | 是 |
| 标准 | 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 |
结果
主要结果指标
1. Incidence of Death From Any Cause or Myocardial Infarction [2.2 years]
2. Cumulative Event Rate of Death From Any Cause or Myocardial Infarction [3 years]
次要成果指标
1. Time to First Occurrence of the Composite of Death, Nonfatal MI, Resuscitated Cardiac Arrest, or Hospitalization for Unstable Angina or Heart Failure [~2.8 year follow-up]
2. Angina Control and Quality of Life, as Assessed by the Seattle Angina Questionnaire Summary Score [~2.8 year follow-up]
3. Time to First Occurrence of the Composite of Death, Nonfatal MI, Hospitalization for Unstable Angina, Hospitalization for Heart Failure, Resuscitated Cardiac Arrest, or Stroke [~2.8 year follow-up]
4. Time to First Occurrence of the Composite of Death, Nonfatal MI, or Stroke [~2.8 year follow-up]
5. Time to First Occurrence of the Composite Endpoints Incorporating Cardiovascular Death [~2.8 year follow-up]
6. Time to First Occurrence of the Composite Endpoints Incorporating Other Definitions of MI as Defined in the Clinical Event Charter [~2.8 year follow-up]
7. Time to First Occurrence of the Individual Components of the Primary and Major Secondary Endpoints [~2.8 year follow-up]
8. Time to First Occurrence of the Stroke [~2.8 year follow-up]
9. Health Resource Utilization, Costs, and Cost Effectiveness [~2.8 year follow-up]
