Benefits of Medical Therapy Plus Stenting for Renal Atherosclerotic Lesions (CORAL)
|Atherosclerosis Cardiovascular Diseases Hypertension, Renovascular Renal Artery Obstruction||Drug: Atacand/HCT, Caduet Procedure: GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting)||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL)|
- Composite Endpoint: Death From Cardiovascular or Renal Causes, Stroke, Myocardial Infarction, Hospitalization for CHF, Progressive Renal Insufficiency, or Permanent Renal Replacement Therapy [ Time Frame: Measured at every 3 months for the first year and annually thereafter ]Only the first event per participant is included in the composite
- Cardiovascular or Renal Death [ Time Frame: Measured at every 3 months for the first year and annually thereafter ]
- Myocardial Infarction [ Time Frame: Measured at every 3 months for the first year and annually thereafter ]
- Hospitalization for Congestive Heart Failure [ Time Frame: Measured at every 3 months for the first year and annually thereafter ]
- Stroke [ Time Frame: Measured at every 3 months for the first year and annually thereafter ]
- 30% Reduction of eGFR From Baseline, Persisting for Greater Than or Equal to 60 Days [ Time Frame: Measured at every 3 months for the first year and annually thereafter ]
- Need for Renal Replacement Therapy [ Time Frame: Measured at every 3 months for the first year and annually thereafter ]
|Study Start Date:||April 2004|
|Study Completion Date:||September 2013|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Active Comparator: Optimal Medical Therapy
Optimal anti-hypertensive therapy
Drug: Atacand/HCT, Caduet
Atacand/HCT and caduet or optimal medical therapy for hypertension
Stent procedure plus optimal anti-hypertensive therapy
Procedure: GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting)
Angioplasty plus stenting of the renal artery GENESISTM Embolic Protection Stent and Angioguard Device
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Atherosclerotic renal artery stenosis is a common problem for which there is no clear consensus on diagnosis or therapy. There likely exists a progression in which renal ischemia leads to neuroendocrine activation, hypertension, and renal insufficiency resulting in acceleration of atherosclerosis, further renal dysfunction, and development of left ventricular hypertrophy. These events in turn lead to adverse clinical events.
Renal artery stenosis is one of the two major known causes of hypertension and occurs in 1-5% of hypertensive patients. In patients with accelerated hypertension, the prevalence of renal artery stenosis is much higher, ranging from 10-40%. Renal artery stenosis, when occurring bilaterally, or in a solitary kidney, is a significant cause for end-stage renal disease, accounting for several percent of patients with end-stage renal disease. Clinically, atherosclerotic renal artery stenosis is a major problem primarily in older patients, and is often seen in long-standing hypertensives whose blood pressure becomes very difficult to control. Of major significance is the progressive nature of atherosclerotic renal artery stenosis, progressing at the rate of about 10% per year (45-60% progression rate in 4-7 year follow-ups). Over this time period, 10-15% of patients develop total renal artery occlusion. If the renal artery stenosis is greater than 75% when detected, 40% of patients develop total occlusion. Due to the progressive nature of atherosclerotic lesions, the decline in renal function in some individuals, and difficult-to-control hypertension, the medical community has sought to detect those patients in whom intervention would be beneficial. This has been extremely difficult to achieve and tests to date have not been uniformly predictive, including peripheral vein plasma renin activity, renal vein renin activity, captopril-stimulated nuclear medicine renal scans, etc.
Since approximately 50% of patients with unilateral renal artery stenosis of significant degree (definitions vary) benefit from surgical intervention, enthusiasm has continued with the advent of renal artery angioplasty. The entire field is moving very quickly. However, there are neither current data nor prospective studies indicating the benefit of renal artery angioplasty plus stents. Studies over the last decade have shown that balloon angioplasty alone is associated with a high rate of recurrence in patients with atherosclerotic renal artery stenosis. In the present climate, there is great enthusiasm to perform angioplasty plus stent placement in atherosclerotic renal artery stenosis, without supporting data for efficacy compared to medical management alone. Angioplasty and stent placement in the renal arteries had been the domain of interventional radiologists, but recently, interventional cardiologists are also performing these procedures. The questions as to who will benefit from intervention and which intervention to use have not been answered. Renal artery angioplasty and stent placement subjects the patient to procedural risks, as well as increased cost, when compared to aggressive antihypertensive medication and risk factor medication and therapy.
This randomized, multicenter clinical trial will contrast the effect of optimal medical therapy alone to stenting with optimal medical therapy, on a composite of cardiovascular and renal endpoints: cardiovascular or renal death, myocardial infarction, hospitalization for congestive heart failure, stroke, doubling of serum creatinine level, and need for renal replacement therapy. These endpoints will be evaluated by a clinical events committee masked to treatment assignment. The secondary endpoints will 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.
Patients will undergo a baseline evaluation to determine eligibility. Approximately 1,080 patients will be randomized to optimal medical therapy alone or to stenting with optimal medical therapy at an estimated 100 clinical sites. Initially, patients will be followed at 2-week intervals, until blood pressure is at target or up to 2 months. Follow-up visits will be mandated at 2 weeks, every 3 months for the first year and annually thereafter. Coordinator visits will also occur semi-annually.
The CORAL Study Chair is Lance Dworkin, MD, Brown University, Providence, RI. The CORAL Study Co-Chair is William Henrich, MD, University of Texas, San Antonio, TX. The Principal Investigators of the CORAL Clinical Coordinating Center are Christopher Cooper, MD, University of Toledo Health Science Campus, Toledo OH, and Timothy Murphy, MD, Brown University, Providence, RI.
The Principal Investigator of the Angiographic Core Laboratory is Alan Matsumoto, MD, University of Virginia, Charlottesville, VA. The Principal Investigator of the GFR and Biochemistry Core Laboratory is Michael Steffes, MD, University of Minnesota, Minneapolis, MN. The Principal Investigator of the Economics and Quality of Life Core Laboratory is David Cohen, MD, Mid-America Heart Institute, St. Luke's Hospital, Kansas City, MO. The Principal Investigator of the Data Coordinating Center is Donald Cutlip, MD, Beth Israel Deaconess Medical Center, Boston, MA. For additional information about the CORAL trial, please refer to the CORAL website (link given below).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00081731
|United States, Ohio|
|University of Toledo|
|Toledo, Ohio, United States, 43614|
|Principal Investigator:||David Cohen, MD||Mid-America Heart Institute, St. Luke's Hospital, Kansas City, MO|
|Principal Investigator:||Christopher J. Cooper, MD||University of Toledo|
|Principal Investigator:||Donald Cutlip, MD||Beth Israel Deaconess Medcial Center|
|Principal Investigator:||Alan Matsumoto, MD||University of Virginia School of Medicine|
|Principal Investigator:||Michael Steffes, MD||University of Minnesota - Clinical and Translational Science Institute|
|Principal Investigator:||Timothy P Murphy, MD||Rhode Island Hospital|
|Study Chair:||Scott D Solomon, MD||Brigham and Women's Hospital|
|Study Chair:||Lance D Dworkin, MD||Rhode Island Hospital|