search
Back to results

Benefits of Medical Therapy Plus Stenting for Renal Atherosclerotic Lesions (CORAL)

Primary Purpose

Atherosclerosis, Cardiovascular Diseases, Hypertension, Renovascular

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Atacand/HCT, Caduet
GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting)
Sponsored by
Baim Institute for Clinical Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atherosclerosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA: Either Documented history of hypertension on two or more anti-hypertensive medications OR Renal dysfunction, defined as Stage 3 or greater chronic kidney disease (CKD) based on the new National Kidney Foundation (NKF) classifications (estimated glomerular filtration rate [GFR] less than 60 mL per minute per 1.73 m^2, calculated by the modified Modification of Diet in Renal Disease [MDRD] formula) One or more severe renal artery stenoses by any of the following pathways: a. Angiographic: greater than or equal to 60% and less than 100% by renal angiogram OR b. Duplex: systolic velocity of greater than 300 cm/sec OR c. Core Lab approved Magnetic Resonance Angiogram (MRA) (refer to the protocol for specific criteria) demonstrating stenosis greater than 80% OR stenosis greater than 70% with spin dephasing on 3D phase contrast MRA OR stenosis greater than 70% and two of the following: i. Ischemic kidney is greater than 1 cm. smaller than contralateral kidney ii. Ischemic kidney enhances less on arterial phase iii. Ischemic kidney has delayed Gd excretion iv. Ischemic kidney hyper-concentrates the urine v. 2-D phase contrast flow waveform shows delayed systolic peak vi. Post-stenotic dilatation d. Clinical index of suspicion combined with a Core Lab approved Computed Tomography Angiography (CTA) demonstrating Stenosis is greater than 80% by visual assessment on high quality CTA Stenosis is greater than 70% on CTA by visual assessment and there are two of the following i. The length of the ischemic kidney is greater than 1 cm. smaller than contralateral kidney ii. Reduced cortical thickness of ischemic kidney iii. Less cortical enhancement of ischemic kidney on arterial phase iv. Post-stenotic dilatation EXCLUSION CRITERIA: Unable to provide informed consent Unable or willing to comply with study protocol or procedures Must be greater than 18 years of age Fibromuscular dysplasia or other non-atherosclerotic renal artery stenosis known to be present prior to randomization Pregnancy or unknown pregnancy status in female of childbearing potential Participation in any drug or device trial during the study period, unless approved by the Steering Committee Prior enrollment in the CORAL study History of stroke within 6 months, if associated with a residual neurologic deficit* Any major surgery, major trauma, revascularization procedure, unstable angina, or myocardial infarction 30 days prior to study entry* Any planned major surgery or revascularization procedure, outside of the randomly allocated renal stenting indicated by the protocol, after randomization* Hospitalization for heart failure within 30 days* Comorbid condition causing life expectancy of less than or equal to 3 years* Allergic reaction to intravascular contrast, not amenable to pre-treatment Allergy to stainless steel Allergy to all of the following: aspirin, clopidogrel, ticlopidine Known untreated aneurysm of the abdominal aorta greater than 5.0 cm.* Previous kidney transplant a. Stenosis of greater than 50% of a previously treated revascularized renal artery OR b. Treatment of any renal artery stenosis within the past 9 months (roll-in patients can have prior treatment on the contralateral side) Kidney size less than 7 cm. supplied by target vessel Hydronephrosis, nephritis or other known cause of renal insufficiency, not due to large vessel renal artery stenosis Visualized stenosis of only an accessory renal artery supplying greater than 1/2 of the ipsilateral renal parenchyma, without stenosis in a dominant renal artery Local lab serum Cr greater than 4.0 mg/dl on the day of randomization* Presence of a renal artery stenosis not amenable for treatment with a stent, known to be present prior to randomization The index lesion cannot be treated with a single stent (i.e. greater than 18 mm. in length) The placement of a stent will necessitate covering a renal artery branch renal artery with a stent The stenosis is in an artery less than 3.5 mm. in diameter The stenosis involves a segmental renal artery branch Abrupt vessel closure or dissection after diagnostic angiography [NOTE: Patients with abrupt vessel closure or dissection as a result of diagnostic angiography will not be randomized but will undergo stent revascularization, receive optimal medical therapy and will be followed for the full study period] *Roll-in patients do not need to meet these inclusion/exclusion criteria

Sites / Locations

  • University of Toledo

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Optimal Medical Therapy

Stenting

Arm Description

Optimal anti-hypertensive therapy

Stent procedure plus optimal anti-hypertensive therapy

Outcomes

Primary Outcome Measures

Composite Endpoint: Death From Cardiovascular or Renal Causes, Stroke, Myocardial Infarction, Hospitalization for CHF, Progressive Renal Insufficiency, or Permanent Renal Replacement Therapy
Only the first event per participant is included in the composite
Cardiovascular or Renal Death
Myocardial Infarction
Hospitalization for Congestive Heart Failure
Stroke
30% Reduction of eGFR From Baseline, Persisting for Greater Than or Equal to 60 Days
Need for Renal Replacement Therapy

Secondary Outcome Measures

Full Information

First Posted
April 19, 2004
Last Updated
September 18, 2015
Sponsor
Baim Institute for Clinical Research
Collaborators
Beth Israel Deaconess Medical Center
search

1. Study Identification

Unique Protocol Identification Number
NCT00081731
Brief Title
Benefits of Medical Therapy Plus Stenting for Renal Atherosclerotic Lesions
Acronym
CORAL
Official Title
Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
April 2004 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baim Institute for Clinical Research
Collaborators
Beth Israel Deaconess Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study will compare medical therapy plus stenting of hemodynamically significant renal artery stenoses versus medical therapy alone in patients with systolic hypertension and renal artery stenosis.
Detailed Description
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 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. DESIGN NARRATIVE: 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atherosclerosis, Cardiovascular Diseases, Hypertension, Renovascular, Renal Artery Obstruction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
947 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Optimal Medical Therapy
Arm Type
Active Comparator
Arm Description
Optimal anti-hypertensive therapy
Arm Title
Stenting
Arm Type
Experimental
Arm Description
Stent procedure plus optimal anti-hypertensive therapy
Intervention Type
Drug
Intervention Name(s)
Atacand/HCT, Caduet
Intervention Description
Atacand/HCT and caduet or optimal medical therapy for hypertension
Intervention Type
Procedure
Intervention Name(s)
GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting)
Intervention Description
Angioplasty plus stenting of the renal artery GENESISTM Embolic Protection Stent and Angioguard Device
Primary Outcome Measure Information:
Title
Composite Endpoint: Death From Cardiovascular or Renal Causes, Stroke, Myocardial Infarction, Hospitalization for CHF, Progressive Renal Insufficiency, or Permanent Renal Replacement Therapy
Description
Only the first event per participant is included in the composite
Time Frame
Measured at every 3 months for the first year and annually thereafter
Title
Cardiovascular or Renal Death
Time Frame
Measured at every 3 months for the first year and annually thereafter
Title
Myocardial Infarction
Time Frame
Measured at every 3 months for the first year and annually thereafter
Title
Hospitalization for Congestive Heart Failure
Time Frame
Measured at every 3 months for the first year and annually thereafter
Title
Stroke
Time Frame
Measured at every 3 months for the first year and annually thereafter
Title
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
Title
Need for Renal Replacement Therapy
Time Frame
Measured at every 3 months for the first year and annually thereafter

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: Either Documented history of hypertension on two or more anti-hypertensive medications OR Renal dysfunction, defined as Stage 3 or greater chronic kidney disease (CKD) based on the new National Kidney Foundation (NKF) classifications (estimated glomerular filtration rate [GFR] less than 60 mL per minute per 1.73 m^2, calculated by the modified Modification of Diet in Renal Disease [MDRD] formula) One or more severe renal artery stenoses by any of the following pathways: a. Angiographic: greater than or equal to 60% and less than 100% by renal angiogram OR b. Duplex: systolic velocity of greater than 300 cm/sec OR c. Core Lab approved Magnetic Resonance Angiogram (MRA) (refer to the protocol for specific criteria) demonstrating stenosis greater than 80% OR stenosis greater than 70% with spin dephasing on 3D phase contrast MRA OR stenosis greater than 70% and two of the following: i. Ischemic kidney is greater than 1 cm. smaller than contralateral kidney ii. Ischemic kidney enhances less on arterial phase iii. Ischemic kidney has delayed Gd excretion iv. Ischemic kidney hyper-concentrates the urine v. 2-D phase contrast flow waveform shows delayed systolic peak vi. Post-stenotic dilatation d. Clinical index of suspicion combined with a Core Lab approved Computed Tomography Angiography (CTA) demonstrating Stenosis is greater than 80% by visual assessment on high quality CTA Stenosis is greater than 70% on CTA by visual assessment and there are two of the following i. The length of the ischemic kidney is greater than 1 cm. smaller than contralateral kidney ii. Reduced cortical thickness of ischemic kidney iii. Less cortical enhancement of ischemic kidney on arterial phase iv. Post-stenotic dilatation EXCLUSION CRITERIA: Unable to provide informed consent Unable or willing to comply with study protocol or procedures Must be greater than 18 years of age Fibromuscular dysplasia or other non-atherosclerotic renal artery stenosis known to be present prior to randomization Pregnancy or unknown pregnancy status in female of childbearing potential Participation in any drug or device trial during the study period, unless approved by the Steering Committee Prior enrollment in the CORAL study History of stroke within 6 months, if associated with a residual neurologic deficit* Any major surgery, major trauma, revascularization procedure, unstable angina, or myocardial infarction 30 days prior to study entry* Any planned major surgery or revascularization procedure, outside of the randomly allocated renal stenting indicated by the protocol, after randomization* Hospitalization for heart failure within 30 days* Comorbid condition causing life expectancy of less than or equal to 3 years* Allergic reaction to intravascular contrast, not amenable to pre-treatment Allergy to stainless steel Allergy to all of the following: aspirin, clopidogrel, ticlopidine Known untreated aneurysm of the abdominal aorta greater than 5.0 cm.* Previous kidney transplant a. Stenosis of greater than 50% of a previously treated revascularized renal artery OR b. Treatment of any renal artery stenosis within the past 9 months (roll-in patients can have prior treatment on the contralateral side) Kidney size less than 7 cm. supplied by target vessel Hydronephrosis, nephritis or other known cause of renal insufficiency, not due to large vessel renal artery stenosis Visualized stenosis of only an accessory renal artery supplying greater than 1/2 of the ipsilateral renal parenchyma, without stenosis in a dominant renal artery Local lab serum Cr greater than 4.0 mg/dl on the day of randomization* Presence of a renal artery stenosis not amenable for treatment with a stent, known to be present prior to randomization The index lesion cannot be treated with a single stent (i.e. greater than 18 mm. in length) The placement of a stent will necessitate covering a renal artery branch renal artery with a stent The stenosis is in an artery less than 3.5 mm. in diameter The stenosis involves a segmental renal artery branch Abrupt vessel closure or dissection after diagnostic angiography [NOTE: Patients with abrupt vessel closure or dissection as a result of diagnostic angiography will not be randomized but will undergo stent revascularization, receive optimal medical therapy and will be followed for the full study period] *Roll-in patients do not need to meet these inclusion/exclusion criteria
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Cohen, MD
Organizational Affiliation
Mid-America Heart Institute, St. Luke's Hospital, Kansas City, MO
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Christopher J. Cooper, MD
Organizational Affiliation
University of Toledo
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Donald Cutlip, MD
Organizational Affiliation
Beth Israel Deaconess Medcial Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alan Matsumoto, MD
Organizational Affiliation
University of Virginia School of Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael Steffes, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Timothy P Murphy, MD
Organizational Affiliation
Rhode Island Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Scott D Solomon, MD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Lance D Dworkin, MD
Organizational Affiliation
Rhode Island Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
University of Toledo
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43614
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16824832
Citation
Cooper CJ, Murphy TP, Matsumoto A, Steffes M, Cohen DJ, Jaff M, Kuntz R, Jamerson K, Reid D, Rosenfield K, Rundback J, D'Agostino R, Henrich W, Dworkin L. Stent revascularization for the prevention of cardiovascular and renal events among patients with renal artery stenosis and systolic hypertension: rationale and design of the CORAL trial. Am Heart J. 2006 Jul;152(1):59-66. doi: 10.1016/j.ahj.2005.09.011.
Results Reference
background
PubMed Identifier
16221898
Citation
Murphy TP, Cooper CJ, Dworkin LD, Henrich WL, Rundback JH, Matsumoto AH, Jamerson KA, D'Agostino RB. The Cardiovascular Outcomes with Renal Atherosclerotic Lesions (CORAL) study: rationale and methods. J Vasc Interv Radiol. 2005 Oct;16(10):1295-300. doi: 10.1097/01.RVI.0000176301.69756.28. No abstract available.
Results Reference
background
PubMed Identifier
24245567
Citation
Bittl JA. Treatment of atherosclerotic renovascular disease. N Engl J Med. 2014 Jan 2;370(1):78-9. doi: 10.1056/NEJMe1313423. Epub 2013 Nov 18. No abstract available.
Results Reference
result
PubMed Identifier
34183258
Citation
Lerman LO. Cell-based regenerative medicine for renovascular disease. Trends Mol Med. 2021 Sep;27(9):882-894. doi: 10.1016/j.molmed.2021.06.004. Epub 2021 Jun 25.
Results Reference
derived
PubMed Identifier
30962703
Citation
Chen T, Brewster P, Tuttle KR, Dworkin LD, Henrich W, Greco BA, Steffes M, Tobe S, Jamerson K, Pencina K, Massaro JM, D'Agostino RB Sr, Cutlip DE, Murphy TP, Cooper CJ, Shapiro JI. Prediction of cardiovascular outcomes with machine learning techniques: application to the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study. Int J Nephrol Renovasc Dis. 2019 Mar 21;12:49-58. doi: 10.2147/IJNRD.S194727. eCollection 2019.
Results Reference
derived
PubMed Identifier
27647847
Citation
Murphy TP, Cooper CJ, Pencina KM, D'Agostino R, Massaro J, Cutlip DE, Jamerson K, Matsumoto AH, Henrich W, Shapiro JI, Tuttle KR, Cohen DJ, Steffes M, Gao Q, Metzger DC, Abernethy WB, Textor SC, Briguglio J, Hirsch AT, Tobe S, Dworkin LD. Relationship of Albuminuria and Renal Artery Stent Outcomes: Results From the CORAL Randomized Clinical Trial (Cardiovascular Outcomes With Renal Artery Lesions). Hypertension. 2016 Nov;68(5):1145-1152. doi: 10.1161/HYPERTENSIONAHA.116.07744. Epub 2016 Sep 19.
Results Reference
derived
PubMed Identifier
26653621
Citation
Murphy TP, Cooper CJ, Matsumoto AH, Cutlip DE, Pencina KM, Jamerson K, Tuttle KR, Shapiro JI, D'Agostino R, Massaro J, Henrich W, Dworkin LD. Renal Artery Stent Outcomes: Effect of Baseline Blood Pressure, Stenosis Severity, and Translesion Pressure Gradient. J Am Coll Cardiol. 2015 Dec 8;66(22):2487-94. doi: 10.1016/j.jacc.2015.09.073.
Results Reference
derived
PubMed Identifier
24903387
Citation
Evans KL, Tuttle KR, Folt DA, Dawson T, Haller ST, Brewster PS, He W, Jamerson K, Dworkin LD, Cutlip DE, Murphy TP, D'Agostino RB Sr, Henrich W, Cooper CJ. Use of renin-angiotensin inhibitors in people with renal artery stenosis. Clin J Am Soc Nephrol. 2014 Jul;9(7):1199-206. doi: 10.2215/CJN.11611113. Epub 2014 Jun 5.
Results Reference
derived
PubMed Identifier
24325931
Citation
Murphy TP, Cooper CJ, Cutlip DE, Matsumoto A, Jamerson K, Rundback J, Rosenfield KA, Henrich W, Shapiro J, Massaro J, Yen CH, Burtch H, Thum C, Reid D, Dworkin L. Roll-in experience from the Cardiovascular Outcomes with Renal Atherosclerotic Lesions (CORAL) study. J Vasc Interv Radiol. 2014 Apr;25(4):511-20. doi: 10.1016/j.jvir.2013.09.018. Epub 2013 Dec 8.
Results Reference
derived
PubMed Identifier
24245566
Citation
Cooper CJ, Murphy TP, Cutlip DE, Jamerson K, Henrich W, Reid DM, Cohen DJ, Matsumoto AH, Steffes M, Jaff MR, Prince MR, Lewis EF, Tuttle KR, Shapiro JI, Rundback JH, Massaro JM, D'Agostino RB Sr, Dworkin LD; CORAL Investigators. Stenting and medical therapy for atherosclerotic renal-artery stenosis. N Engl J Med. 2014 Jan 2;370(1):13-22. doi: 10.1056/NEJMoa1310753. Epub 2013 Nov 18.
Results Reference
derived

Learn more about this trial

Benefits of Medical Therapy Plus Stenting for Renal Atherosclerotic Lesions

We'll reach out to this number within 24 hrs