Is Spironolactone Safe and Effective in the Treatment of Cardiovascular Disease in Mild Chronic Renal Failure? - Full Text View

Sponsor:	University Hospital Birmingham
Collaborator:	British Heart Foundation
Information provided by:	University Hospital Birmingham
ClinicalTrials.gov Identifier:	NCT00291720

Purpose

Patients with kidney failure have a poor survival rate that is due to a much higher than average rate of heart and vascular disease. The reason that kidney failure causes heart disease is unknown but recent research suggests that a hormone called aldosterone, which is increased in patients with kidney disease may damage the heart and blood vessels.

The investigators propose, using a randomized blinded trial, to find out whether drugs that inhibit the actions of aldosterone have beneficial effects on the cardiovascular system in patients with kidney failure

Condition	Intervention	Phase
Chronic Kidney Disease Cardiovascular Disease	Drug: Spironolactone Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Is Spironolactone Safe and Effective in the Treatment of Cardiovascular Disease in Mild Chronic Renal Failure?

Resource links provided by NLM:

MedlinePlus related topics: Kidney Failure

Drug Information available for: Spironolactone

U.S. FDA Resources

Further study details as provided by University Hospital Birmingham:

Primary Outcome Measures:

Changes in left ventricular mass on cardiac MRI and arterial stiffness (assessed by pulse wave velocity). [ Time Frame: 9 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Changes in aortic distensibility and large vessel augmentation [ Time Frame: 9 months ] [ Designated as safety issue: No ]

Enrollment:	120
Study Start Date:	April 2005
Study Completion Date:	December 2007
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Spironolactone: Active Comparator 25mg spironolactone daily	Drug: Spironolactone All patients receive a 4 week open labeled run in phase of 25mg spironolactone daily after which they are randomized to continue or receive matched placebo for 8 months.
Placebo: Placebo Comparator matching placebo medication for the control group	Drug: Placebo matching placebo

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Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Mild-moderate chronic kidney disease (glomerular filtration rate [GFR] 40-80 mls/min calculated by Cockroft-Gault equation)
Controlled blood pressure (< 130/80 mmHg)
On established (> 6 weeks) treatment with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs).

Exclusion Criteria:

Diabetes mellitus
Clinical evidence of fluid overload or hypovolaemia
Recent (< 2 months) acute myocardial infarction
Left ventricular (LV) dysfunction (ejection fraction < 40% by echocardiography).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00291720

Locations

United Kingdom, West Midlands
University Hospital Birmingham
Birmingham, West Midlands, United Kingdom, B15 2TH

Sponsors and Collaborators

University Hospital Birmingham

British Heart Foundation

Investigators

Principal Investigator:

John N Townend, BSc, MB ChB, MD, FRCP, FESC

University Hospital Birmingham

More Information

Publications:

Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 1998 Nov;32(5 Suppl 3):S112-9. Review. No abstract available.

Culleton BF, Larson MG, Wilson PW, Evans JC, Parfrey PS, Levy D. Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency. Kidney Int. 1999 Dec;56(6):2214-9.

Coulden RA, Moss H, Graves MJ, Lomas DJ, Appleton DS, Weissberg PL. High resolution magnetic resonance imaging of atherosclerosis and the response to balloon angioplasty. Heart. 2000 Feb;83(2):188-91.

Thambyrajah J, Landray MJ, McGlynn FJ, Jones HJ, Wheeler DC, Townend JN. Does folic acid decrease plasma homocysteine and improve endothelial function in patients with predialysis renal failure? Circulation. 2000 Aug 22;102(8):871-5.

Landray MJ, Thambyrajah J, McGlynn FJ, Jones HJ, Baigent C, Kendall MJ, Townend JN, Wheeler DC. Epidemiological evaluation of known and suspected cardiovascular risk factors in chronic renal impairment. Am J Kidney Dis. 2001 Sep;38(3):537-46.

Jardine AG, McLaughlin K. Cardiovascular complications of renal disease. Heart. 2001 Oct;86(4):459-66. Review. No abstract available.

Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000 Jan 20;342(3):145-53. Erratum in: 2000 May 4;342(18):1376. N Engl J Med 2000 Mar 9;342(10):748.

Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999 Sep 2;341(10):709-17.

Brown NJ. Eplerenone: cardiovascular protection. Circulation. 2003 May 20;107(19):2512-8. Review.

Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M; Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003 Apr 3;348(14):1309-21. Epub 2003 Mar 31. Erratum in: N Engl J Med. 2003 May 29;348(22):2271.

Rocha R, Stier CT Jr, Kifor I, Ochoa-Maya MR, Rennke HG, Williams GH, Adler GK. Aldosterone: a mediator of myocardial necrosis and renal arteriopathy. Endocrinology. 2000 Oct;141(10):3871-8.

Sato T, Nishinaga M, Kawamoto A, Ozawa T, Takatsuji H. Accuracy of a continuous blood pressure monitor based on arterial tonometry. Hypertension. 1993 Jun;21(6 Pt 1):866-74.

Epstein M. Aldosterone as a determinant of cardiovascular and renal dysfunction. J R Soc Med. 2001 Aug;94(8):378-83. Review. No abstract available.

Foley RN, Parfrey PS, Kent GM, Harnett JD, Murray DC, Barre PE. Serial change in echocardiographic parameters and cardiac failure in end-stage renal disease. J Am Soc Nephrol. 2000 May;11(5):912-6.

London GM, Guerin AP, Marchais SJ, Pannier B, Safar ME, Day M, Metivier F. Cardiac and arterial interactions in end-stage renal disease. Kidney Int. 1996 Aug;50(2):600-8.

Guerin AP, Blacher J, Pannier B, Marchais SJ, Safar ME, London GM. Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure. Circulation. 2001 Feb 20;103(7):987-92.

Wilkinson IB, Fuchs SA, Jansen IM, Spratt JC, Murray GD, Cockcroft JR, Webb DJ. Reproducibility of pulse wave velocity and augmentation index measured by pulse wave analysis. J Hypertens. 1998 Dec;16(12 Pt 2):2079-84.

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Edwards NC, Steeds RP, Stewart PM, Ferro CJ, Townend JN. Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease: a randomized controlled trial. J Am Coll Cardiol. 2009 Aug 4;54(6):505-12.

Edwards NC, Ferro CJ, Townend JN, Steeds RP. Aortic distensibility and arterial-ventricular coupling in early chronic kidney disease: a pattern resembling heart failure with preserved ejection fraction. Heart. 2008 Aug;94(8):1038-43. Epub 2008 Feb 28.

Responsible Party:	University Hospital Birmingham ( Research & Development Office )
Study ID Numbers:	RPK2749, 04/Q2707/294
Study First Received:	February 13, 2006
Last Updated:	May 20, 2008
ClinicalTrials.gov Identifier:	NCT00291720 History of Changes
Health Authority:	United Kingdom: Research Ethics Committee

Keywords provided by University Hospital Birmingham:

Aldosterone
Spironolactone
Chronic Kidney Disease
Arterial Stiffness

Additional relevant MeSH terms:

Renal Insufficiency
Hormone Antagonists
Diuretics
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Kidney Failure, Chronic
Cardiovascular Agents
Pharmacologic Actions
Spironolactone

Urologic Diseases
Aldosterone Antagonists
Renal Insufficiency, Chronic
Natriuretic Agents
Therapeutic Uses
Cardiovascular Diseases
Kidney Diseases
Kidney Failure

ClinicalTrials.gov processed this record on November 09, 2009