Benefits of Medical Therapy Plus Stenting for Renal Atherosclerotic Lesions

NCT00081731 | Completed Phase 3 Results DMC

• 2 other identifiers: 161U01HL071556
• Study Type: interventional
• Target: 947
• Locations: 1 country
• Sites: 1

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.

Conditions

Atherosclerosis; Cardiovascular Diseases; Hypertension, Renovascular; Renal Artery Obstruction

Outcome Measures

Primary Outcomes (7)

• 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 at every 3 months for the first year and annually thereafter

• Cardiovascular or Renal Death

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

• Myocardial Infarction

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

• Hospitalization for Congestive Heart Failure

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

• Stroke

  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

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

• Need for Renal Replacement Therapy

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

Study Arms (2)

Optimal Medical Therapy

ACTIVE COMPARATOR

Optimal anti-hypertensive therapy

Drug: Atacand/HCT, Caduet

Stenting

EXPERIMENTAL

Stent procedure plus optimal anti-hypertensive therapy

Procedure: GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting)

Interventions

Atacand/HCT, Caduet DRUG

Atacand/HCT and caduet or optimal medical therapy for hypertension

Optimal Medical Therapy

GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting) PROCEDURE

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

Stenting

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baim Institute for Clinical Research: lead
• Beth Israel Deaconess Medical Center: collaborator

Study Sites (1)

University of Toledo

Toledo, Ohio, 43614, United States

Location

Related Publications (11)

• 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.

  PMID: 16824832 BACKGROUND

• 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.

  PMID: 16221898 BACKGROUND

• 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.

  PMID: 24245567 RESULT

• 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.

  PMID: 39402005 DERIVED

• 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.

  PMID: 34183258 DERIVED

• 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.

  PMID: 30962703 DERIVED

• 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.

  PMID: 27647847 DERIVED

• 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.

  PMID: 26653621 DERIVED

• 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.

  PMID: 24903387 DERIVED

• 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.

  PMID: 24325931 DERIVED

• 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.

  PMID: 24245566 DERIVED

MeSH Terms

Conditions

Atherosclerosis; Cardiovascular Diseases; Hypertension, Renovascular; Renal Artery Obstruction

Interventions

amlodipine, atorvastatin drug combination; Angioplasty; Stents

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Hypertension, Renal; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hypertension

Intervention Hierarchy (Ancestors)

Catheterization; Therapeutics; Endovascular Procedures; Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Investigative Techniques; Prostheses and Implants; Equipment and Supplies

Limitations and Caveats

Patients could be enrolled in the trial with renal artery stenosis \> = 60%. Didn't include patients with fibromuscular dysplasia. Some screened and deemed to be eligible were not enrolled because of physician preference.

Results Point of Contact

• Title: Christopher Cooper, MD
• Organization: University of Toledo

christopher.cooper@utoledo.edu

419-383-6297

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

• Timothy P Murphy, MD

  Rhode Island Hospital

  PRINCIPAL INVESTIGATOR

• Scott D Solomon, MD

  Brigham and Women's Hospital

  STUDY CHAIR

• Lance D Dworkin, MD

  Rhode Island Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2004
• First Posted: April 21, 2004
• Study Start: April 1, 2004
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: October 5, 2015
• Results First Posted: January 29, 2014

Record last verified: 2015-09

Locations

US (1)