Cardiovascular Outcomes in Renal Atherosclerotic Lesions [CORAL] Randomized and Multi-Center Two-Group Clinical Trial To Assess The Best Treatment for Patients with High Blood Pressure and Renal Artery Stenosis: Stenting with Anti-Hypertensive Medical Therapy, Compared to Medical Therapy Alone
This study will enroll patients with a history of systolic hypertension, who have documented renal artery stenosis. Patients will be randomized to either medical therapy or medical therapy with renal artery stenting and be closely monitored for blood pressure control and management of other risk factors.
All patients will have quality of life measures performed, and cost effectiveness data will be collected for analysis.
A total of 1080 patients from 100 sites in the United States and 100 sites outside of the United States will be included in this study. This study is designed to compare the safety and effectiveness of treating renal artery stenosis with the use of a system including an investigational device and blood pressure medication as compared to blood pressure medication alone. All subjects will also be invited to participate in the genetic sub-study, which is optional. This research is necessary because more information is needed to help determine why some patients respond differently to the effects of hypertension and renal artery stenosis. One-tablespoon blood from a vein and urine will be collected at the baseline visit. This will be a one-time sample but we may ask for a second blood sample if the research laboratory cannot process the first sample. NHLBI, The University of Toledo will store the DNA samples until it is all gone, or until they decide to discard the sample. The sponsor is providing a “certificate of confidentiality” for all sites.
The study drugs used to treat participants randomized to drug therapy are Candesartan (Atacand) or Candesartan (Atacand)/ HCT (Hydrochlorothiazide). They are FDA approved medications for the treatment of hypertension. The drug Caduet will also be provided. It is a combination drug (amlodipine besylate and atorvastatin), which is approved by the FDA for the treatment of hypertension and high cholesterol.
The participant’s overall health will be closely monitored by the Investigator in conjunction with collaborating with the participant’s primary care physician for the management of their diabetes, hypertension, and lipid control.
Participants that are randomized to medical treatment alone that requires stenting will be considered as “cross-overs”. However, if the participant meets all of the following criteria before a stent is placed, the cross-over procedure will not constitute a protocol deviation : 1) patient presents with anuric acute renal failure; 2) complete occlusion of all arteries to the one kidney if there is a solitary kidney or complete occlusion of all arteries to both kidneys if there are two kidneys documented angiographically, and 3) there is at least one kidney distal to a complete occlusion that is greater that 8 cm in length.
Quality of life assessments will be completed by participants that will evaluate relative cost-effectiveness of the 2 treatment groups. The 36 item Short-Form Health Survey (SF-36 and the EuroQOL health status instrument (EQ-5D) will be used to measure treatment-related side effects. The questionnaires will be performed at baseline, 6-months, years 1, 2, and 3, and closeout.
Males/females >18 years of age, and either:
• Documented history hypertension on 2 or more anti-hypertensive medications OR
• Renal dysfunction defined as Stage 3 or greater CKD based on the new NKF classification (estimated GFR, <60ml per minute per 1.7m² calculated by the modified MDRD formula)
One or more severe renal artery stenoses by any of the following pathways:
• Angiographic: > 60% and <100 % by renal angiogram OR
• Duplex: systolic velocity of > 300 cm/sec OR
• Core lab approved MRA demonstrating:
1. stenosis >80%, OR
2. stenosis > 70% with spin dephasing on 3D phase contrast MRA OR
3. stenosis > 70% and two of the following:
• ischemic kidney is >1 cm smaller than contralateral kidney
• ischemic kidney enhances less on arterial phase
• ischemic kidney has delayed Gd excretion
• ischemic kidney hyper-concentrates the urine
• 2-D phase contrast flow waveform shows delayed systolic peak
• Post-stenotic dilatation
4. Clinical index of suspicion combined with a core lab approved CTA demonstrating:
• Stenosis is >80% by visual assessment on high quality CTA
• Stenosis is >70% on CTA by visual assessment and there are two of the following:
o The length of ischemic kidney is >1 cm smaller than contralateral kidney
o Reduced cortical thickness of ischemic kidney
o Less cortical enhancement of ischemic kidney on arterial phase
o Post-stenotic dilatation