To compare (a) medical therapy plus stenting of hemodynamically significant renal artery stenoses and (b) medical therapy alone in patients with systolic hypertension and renal artery stenosis.

Condition	Treatment or Intervention	Phase
Atherosclerosis Cardiovascular Diseases Hypertension, Renovascular Renal Artery Obstruction	Drug: Antihypertensive Agents  Procedure: Angioplasty  Device: Stent	Phase III

Further Study Details: 

BACKGROUND: 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 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 and ultimately death.

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% progressive 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, decline in renal function in some, 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 is 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 now approaching these lesions with angioplasty and stent. 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 increasing the cost, when compared to aggressive antihypertensive medication and risk factor medication and therapy.

DESIGN NARRATIVE: The randomized, multicenter clinical trial contrasts 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.

Approximately 2,200 patients will undergo a baseline evaluation with randomization of 1,080 patients to optimum medical therapy alone or to stenting with optimum medical therapy at an estimated 65 clinical sites. Initially, patients will be followed at two-week intervals, until blood pressure is at target or up to two months. Follow-up visits will be mandated at two weeks, every three months for the first year and annually thereafter. Coordinator visits will also occur semi-annually.

The CORAL Study Chair is Lance Dworkin, M.D., Brown University, Providence, RI. The CORAL Study Co-Chair is William Henrich, M.D., University of Maryland, Baltimore, MD. The Principal Investigators of the CORAL Clinical Coordinating Center are Christopher Cooper, M.D., Medical College of Ohio, Toledo OH, and Timothy Murphy, M.D., Brown University, Providence, RI. The Principal Investigator of the Angiographic Core Laboratory is Alan Matsumoto, M.D., University of Virginia, Charlottesville, VA. The Principal Investigator of the GFR and Biochemistry Core Laboratory is Michael Steffes, M.D., University of Minnesota, Minneapolis, MN. The Principal Investigator of the Economics and Quality of Life Core Laboratory is David Cohen, M.D., Beth Israel Deaconess Hospital, Boston, MA. The Principal Investigator of the Data Coordinating Center is Richard Kuntz, M.D., Brigham & Women's Hospital, Boston, MA. For additional information about the CORAL trial, please refer to the CORAL website (URL listed below).

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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.

Ohio
      Medical College of Ohio, Toledo,  Ohio,  43614,  United States; Recruiting

Study chairs or principal investigators

David Cohen,  Beth Israel Deaconess Medical Center   
Christopher Cooper,  Medical College of Ohio   
Richard Kuntz,  Brigham and Women's Hospital   
Alan Matsumoto,  University of Virginia School of Medicine   
Michael Steffes,  University of Minnesota, Twin Cities   

Study ID Numbers:  161
Record last reviewed:  February 2005
Last Updated:  February 17, 2005
Record first received:  April 19, 2004
ClinicalTrials.gov Identifier:  NCT00081731
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08