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AtherosclerosisPhase 3CORALNCT00081731

Benefits of Medical Therapy Plus Stenting for Renal Atherosclerotic Lesions

A Phase 3 study testing Atacand/HCT, Caduet and GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting) in people with Atherosclerosis and Cardiovascular Diseases, run by Baim Institute for Clinical Research at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Atacand/HCT, Caduet and GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting)
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
947 participants
Where
1 siteUnited States
Study dates
Apr 2004to Sep 2013
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 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

Who cannot join

  • 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
Show all 28Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Toledo

    Toledo, Ohio, 43614

Other trials in United States

About this study

Official title: Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL)

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.

Read the 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).

Being tested
Atacand/HCT, Caduet, GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting)
Medical subject headings
Atherosclerosis, Cardiovascular Diseases, Hypertension, Renovascular, Renal Artery Obstruction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Atacand/HCT, CaduetDrug

    Atacand/HCT and caduet or optimal medical therapy for hypertension

  • GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting)Procedure or surgery

    Angioplasty plus stenting of the renal artery GENESISTM Embolic Protection Stent and Angioguard Device

Study groups in NCT00081731
Study groupRoleWhat they receive
Optimal Medical TherapyActive comparatorOptimal anti-hypertensive therapy
Receives: Drug: Atacand/HCT, Caduet
StentingExperimentalStent procedure plus optimal anti-hypertensive therapy
Receives: Procedure: GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Measured at every 3 months for the first year and annually thereafter

  2. Cardiovascular or Renal Death

    Measured: Measured at every 3 months for the first year and annually thereafter

  3. Myocardial Infarction

    Measured: Measured at every 3 months for the first year and annually thereafter

  4. Hospitalization for Congestive Heart Failure

    Measured: Measured at every 3 months for the first year and annually thereafter

  5. Stroke

    Measured: Measured at every 3 months for the first year and annually thereafter

  6. 30% Reduction of eGFR From Baseline, Persisting for Greater Than or Equal to 60 Days

    Measured: Measured at every 3 months for the first year and annually thereafter

  7. Need for Renal Replacement Therapy

    Measured: Measured at every 3 months for the first year and annually thereafter

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Apr 2004 (estimated)
  2. Study startApr 2004
  3. Primary completionSep 2013
  4. Study completionSep 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
947 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00081731
Sponsor's protocol ID
161
Other IDs
U01HL071556
Acronym
CORAL
Status last verified
Sep 2015
First submitted
19 Apr 2004
Last updated
5 Oct 2015
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 16824832
  • 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.

    PubMed 16221898
  • 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.

    PubMed 24245567
  • Arnold SV, Wang K, Kirtane AJ, Magnuson EA, Chinnakondepalli KM, Cooper CJ, Dworkin LD, Cohen DJ. Quality of life effects of renal artery stenting versus medical therapy for atherosclerotic renal-artery stenosis: results from the randomized CORAL trial. Eur Heart J Qual Care Clin Outcomes. 2025 Dec 19;11(8):1388-1395. doi: 10.1093/ehjqcco/qcae087.

    PubMed 39402005
  • 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.

    PubMed 34183258
  • 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.

    PubMed 30962703
  • 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.

    PubMed 27647847
  • 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.

    PubMed 26653621
  • 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.

    PubMed 24903387
  • 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.

    PubMed 24325931
  • 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.

    PubMed 24245566

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Atacand/HCT, Caduet and GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting) in people with Atherosclerosis and Cardiovascular Diseases, run by Baim Institute for Clinical Research at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00081731, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2015.

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