Health-relatedness and Long-term Objectives: Atherosclerotic renal artery stenosis is a common problem for which there is no clear consensus on diagnosis or therapy. There likely exists a progression wherein renal ischemia leads to neuroendocdne activation, hypertension, and renal insufficiency potentially resulting in acceleration of therosclerosis, further renal dysfunction, myocardial infarction, stroke and death. The current proposal tests whether revascularization of a stenotic renal artery plus optimum medical therapy is associated with improved clinical outcomes when compared with optimum medical therapy alone.
Specific Aims, Design and Methods: Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) is a randomized clinical trial that will contrast the effect of optimum medical therapy alone to stenting with optimum medical therapy, on a composite cardiovascular and renal endpoint: cardiovascular or renal death, myocardial infarction, hospitalization for congestive heart failure, stroke, doubling of serum creatinine level, and need for renal replacement therapy. This endpoint will be adjudicated by a clinical events committee masked to treatment assignment. The secondary endpoints 1) evaluate the mechanisms linked to clinical events;2) describe differential effectiveness in critical end-organs;3) determine the value of stenting from the patient and the health policy perspectives, measured as quality of life and cost effectiveness;and 4) evaluate for clinically relevant differences in treatment effectiveness within the primary endpoint. The primary entry criteria are an atherosclerotic renal stenosis >60% with a 20 mmHg systolic pressure gradient and systolic hypertension >155 mmHg on 2 or more anti-hypertensive medications. A slight predominance of women is expected, and high priority will be placed on minority recruitment. Approximately 2200 patients will undergo a baseline evaluation with randomization occurring in 1080. The study has 90% power to detect a 28% reduction in primary endpoint hazard rate. This R01 from the Clinical Coordinating Center describes the main study hypotheses and overall trial conduct.
|Tuttle, Katherine R; Dworkin, Lance D; Henrich, William et al. (2016) Effects of Stenting for Atherosclerotic Renal Artery Stenosis on eGFR and Predictors of Clinical Events in the CORAL Trial. Clin J Am Soc Nephrol 11:1180-8|
|Ren, Kaili; Drummond, Christopher A; Brewster, Pamela S et al. (2016) An alternative empirical likelihood method in missing response problems and causal inference. Stat Med 35:5009-5028|
|Murphy, Timothy P; Cooper, Christopher J; Matsumoto, Alan H et al. (2015) Renal Artery Stent Outcomes: Effect of Baseline Blood Pressure, Stenosis Severity, and Translesion Pressure Gradient. J Am Coll Cardiol 66:2487-94|
|Folt, David A; Evans, Kaleigh L; Brahmandam, Sravya et al. (2015) Regional and physician specialty-associated variations in the medical management of atherosclerotic renal-artery stenosis. J Am Soc Hypertens 9:443-52|
|Hendricks, Nicholas J; Matsumoto, Alan H; Angle, John F et al. (2014) Is fibromuscular dysplasia underdiagnosed? A comparison of the prevalence of FMD seen in CORAL trial participants versus a single institution population of renal donor candidates. Vasc Med 19:363-7|
|Cooper, Christopher J; Murphy, Timothy P; Cutlip, Donald E et al. (2014) Stenting and medical therapy for atherosclerotic renal-artery stenosis. N Engl J Med 370:13-22|
|Murphy, Timothy P; Cooper, Christopher J; Cutlip, Donald E et al. (2014) Roll-in experience from the Cardiovascular Outcomes with Renal Atherosclerotic Lesions (CORAL) study. J Vasc Interv Radiol 25:511-20|
|Evans, Kaleigh L; Tuttle, Katherine R; Folt, David A et al. (2014) Use of renin-angiotensin inhibitors in people with renal artery stenosis. Clin J Am Soc Nephrol 9:1199-206|