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

• ClinicalTrials.gov Identifier: NCT00081731
• Recruitment Status: Completed
• First Posted: April 21, 2004
• Results First Posted: January 29, 2014
• Last Update Posted: October 5, 2015
• Sponsor: Baim Institute for Clinical Research
• Collaborator: Beth Israel Deaconess Medical Center
• Information provided by (Responsible Party): Baim Institute for Clinical Research

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Atherosclerosis; Cardiovascular Diseases; Hypertension, Renovascular; Renal Artery Obstruction
• Interventions: Drug: Atacand/HCT, Caduet; Procedure: GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting)
• Enrollment: 947

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Optimal Medical Therapy	Stenting
Arm/Group Description	Optimal anti-hypertensive therapy Atacand/HCT, Caduet: Atacand/HCT and caduet or optimal medical therapy for hypertension	Stent procedure plus optimal anti-hypertensive therapy GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting): Angioplasty plus stenting of the renal artery GENESISTM Embolic Protection Stent and Angioguard Device
Period Title: Overall Study
Started	480	467
Completed	472	459
Not Completed	8	8
Reason Not Completed
scientific integrity issue	8	8

Baseline Characteristics

Arm/Group Title		Optimal Medical Therapy	Stenting	Total
Arm/Group Description		Optimal anti-hypertensive therapy Atacand/HCT, Caduet: Atacand/HCT and caduet or optimal medical therapy for hypertension	Stent procedure plus optimal anti-hypertensive therapy GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting): Angioplasty plus stenting of the renal artery GENESISTM Embolic Protection Stent and Angioguard Device	Total of all reporting groups
Overall Number of Baseline Participants		472	459	931
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	472 participants	459 participants	931 participants
		69 (9.0)	69.3 (9.4)	69.15 (9.2)
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	472 participants	459 participants	931 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	140 29.7%	127 27.7%	267 28.7%
	>=65 years	332 70.3%	332 72.3%	664 71.3%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	472 participants	459 participants	931 participants
	Female	241 51.1%	225 49.0%	466 50.1%
	Male	231 48.9%	234 51.0%	465 49.9%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	472 participants	459 participants	931 participants
		387	385	772

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optimal Medical Therapy	Stenting
Arm/Group Description:	Optimal anti-hypertensive therapy Atacand/HCT, Caduet: Atacand/HCT and caduet or optimal medical therapy for hypertension	Stent procedure plus optimal anti-hypertensive therapy GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting): Angioplasty plus stenting of the renal artery GENESISTM Embolic Protection Stent and Angioguard Device
Overall Number of Participants Analyzed	472	459
Measure Type: Number; Unit of Measure: participants
	169	161

2. Primary Outcome

Title	Cardiovascular or Renal Death
Description	[Not Specified]
Time Frame	Measured at every 3 months for the first year and annually thereafter

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optimal Medical Therapy	Stenting
Arm/Group Description:	Optimal anti-hypertensive therapy Atacand/HCT, Caduet: Atacand/HCT and caduet or optimal medical therapy for hypertension	Stent procedure plus optimal anti-hypertensive therapy GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting): Angioplasty plus stenting of the renal artery GENESISTM Embolic Protection Stent and Angioguard Device
Overall Number of Participants Analyzed	472	459
Measure Type: Number; Unit of Measure: participants
	20	20

3. Primary Outcome

Title	Myocardial Infarction
Description	[Not Specified]
Time Frame	Measured at every 3 months for the first year and annually thereafter

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optimal Medical Therapy	Stenting
Arm/Group Description:	Optimal anti-hypertensive therapy Atacand/HCT, Caduet: Atacand/HCT and caduet or optimal medical therapy for hypertension	Stent procedure plus optimal anti-hypertensive therapy GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting): Angioplasty plus stenting of the renal artery GENESISTM Embolic Protection Stent and Angioguard Device
Overall Number of Participants Analyzed	472	459
Measure Type: Number; Unit of Measure: participants
	27	30

4. Primary Outcome

Title	Hospitalization for Congestive Heart Failure
Description	[Not Specified]
Time Frame	Measured at every 3 months for the first year and annually thereafter

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optimal Medical Therapy	Stenting
Arm/Group Description:	Optimal anti-hypertensive therapy Atacand/HCT, Caduet: Atacand/HCT and caduet or optimal medical therapy for hypertension	Stent procedure plus optimal anti-hypertensive therapy GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting): Angioplasty plus stenting of the renal artery GENESISTM Embolic Protection Stent and Angioguard Device
Overall Number of Participants Analyzed	472	459
Measure Type: Number; Unit of Measure: participants
	26	27

5. Primary Outcome

Title	Stroke
Description	[Not Specified]
Time Frame	Measured at every 3 months for the first year and annually thereafter

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optimal Medical Therapy	Stenting
Arm/Group Description:	Optimal anti-hypertensive therapy Atacand/HCT, Caduet: Atacand/HCT and caduet or optimal medical therapy for hypertension	Stent procedure plus optimal anti-hypertensive therapy GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting): Angioplasty plus stenting of the renal artery GENESISTM Embolic Protection Stent and Angioguard Device
Overall Number of Participants Analyzed	472	459
Measure Type: Number; Unit of Measure: participants
	16	12

6. Primary Outcome

Title	30% Reduction of eGFR From Baseline, Persisting for Greater Than or Equal to 60 Days
Description	[Not Specified]
Time Frame	Measured at every 3 months for the first year and annually thereafter

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optimal Medical Therapy	Stenting
Arm/Group Description:	Optimal anti-hypertensive therapy Atacand/HCT, Caduet: Atacand/HCT and caduet or optimal medical therapy for hypertension	Stent procedure plus optimal anti-hypertensive therapy GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting): Angioplasty plus stenting of the renal artery GENESISTM Embolic Protection Stent and Angioguard Device
Overall Number of Participants Analyzed	472	459
Measure Type: Number; Unit of Measure: participants
	77	68

7. Primary Outcome

Title	Need for Renal Replacement Therapy
Description	[Not Specified]
Time Frame	Measured at every 3 months for the first year and annually thereafter

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optimal Medical Therapy	Stenting
Arm/Group Description:	Optimal anti-hypertensive therapy Atacand/HCT, Caduet: Atacand/HCT and caduet or optimal medical therapy for hypertension	Stent procedure plus optimal anti-hypertensive therapy GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting): Angioplasty plus stenting of the renal artery GENESISTM Embolic Protection Stent and Angioguard Device
Overall Number of Participants Analyzed	472	459
Measure Type: Number; Unit of Measure: participants
	3	4

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Optimal Medical Therapy		Stenting
Arm/Group Description	Optimal anti-hypertensive therapy Atacand/HCT, Caduet: Atacand/HCT and caduet or optimal medical therapy for hypertension		Stent procedure plus optimal anti-hypertensive therapy GENESISTM Embolic Protection Stent and Angioguard Device (Angioplasty plus stenting): Angioplasty plus stenting of the renal artery GENESISTM Embolic Protection Stent and Angioguard Device
All-Cause Mortality
	Optimal Medical Therapy		Stenting
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Optimal Medical Therapy		Stenting
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	283/472 (59.96%)		290/459 (63.18%)
Blood and lymphatic system disorders
Blood and Lymphatic System Disorders † 1	11/472 (2.33%)	11	16/459 (3.49%)	16
Cardiac disorders
Cardiac Disorders † 1	117/472 (24.79%)	117	128/459 (27.89%)	128
Congenital, familial and genetic disorders
Congenital, Familial and Genetic Disorders † 1	1/472 (0.21%)	1	0/459 (0.00%)	0
Ear and labyrinth disorders
Ear and Labyrinth Disorders † 1	5/472 (1.06%)	5	1/459 (0.22%)	1
Eye disorders
Eye Disorders † 1	3/472 (0.64%)	3	2/459 (0.44%)	2
Gastrointestinal disorders
Gastrointestinal Disorders † 1	42/472 (8.90%)	42	57/459 (12.42%)	57
General disorders
General Disorders † 1	38/472 (8.05%)	38	36/459 (7.84%)	36
Hepatobiliary disorders
Hepatobiliary Disorders † 1	7/472 (1.48%)	7	5/459 (1.09%)	5
Immune system disorders
Immune System Disorders † 1	0/472 (0.00%)	0	1/459 (0.22%)	1
Infections and infestations
Infections and Infestations † 1	69/472 (14.62%)	69	63/459 (13.73%)	63
Injury, poisoning and procedural complications
Injury, Poisoning and Procedural Complications † 1	19/472 (4.03%)	19	42/459 (9.15%)	42
Investigations
Investigations † 1	1/472 (0.21%)	1	4/459 (0.87%)	4
Metabolism and nutrition disorders
Metabolism and Nutrition Disorders † 1	28/472 (5.93%)	28	19/459 (4.14%)	19
Musculoskeletal and connective tissue disorders
Musuloskeletal and Connective Tissue Disorders † 1	31/472 (6.57%)	31	39/459 (8.50%)	39
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms Benign, Malignant and Unspecified † 1	26/472 (5.51%)	26	27/459 (5.88%)	27
Nervous system disorders
Nervous System Disorders † 1	67/472 (14.19%)	67	61/459 (13.29%)	61
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Optimal Medical Therapy		Stenting
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	441/472 (93.43%)		429/459 (93.46%)
Blood and lymphatic system disorders
Blood and Lymphatic System Disorders † 1	93/472 (19.70%)	93	85/459 (18.52%)	85
Cardiac disorders
Cardiac Disorders † 1	205/472 (43.43%)	205	201/459 (43.79%)	201
Ear and labyrinth disorders
Ear and Labyrinth Disorders † 1	24/472 (5.08%)	24	32/459 (6.97%)	32
Eye disorders
Eye Disorders † 1	63/472 (13.35%)	63	60/459 (13.07%)	60
General disorders
General Disorders † 1	261/472 (55.30%)	261	251/459 (54.68%)	251
Injury, poisoning and procedural complications
Injury, Poisoning and Procedural Complications † 1	122/472 (25.85%)	122	133/459 (28.98%)	133
Investigations
Investigations † 1	125/472 (26.48%)	125	124/459 (27.02%)	124
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA

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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Christopher Cooper, MD
• Organization: University of Toledo
• Phone: 419-383-6297
• EMail: christopher.cooper@utoledo.edu

Publications of Results:

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.

Other 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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Review.

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.

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. Epub 2016 Sep 19.

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.

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.

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.

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.

• Responsible Party: Baim Institute for Clinical Research
• ClinicalTrials.gov Identifier: NCT00081731
• Other Study ID Numbers: 161; U01HL071556 ( U.S. NIH Grant/Contract )
• First Submitted: April 19, 2004
• First Posted: April 21, 2004
• Results First Submitted: December 9, 2013
• Results First Posted: January 29, 2014
• Last Update Posted: October 5, 2015