PIE II: Pharmacological Intervention in the Elderly II - Full Text View

Sponsored by:	National Institute on Aging (NIA)
Information provided by:	National Institute on Aging (NIA)
ClinicalTrials.gov Identifier:	NCT00123955

Purpose

The purpose of this study is to examine whether spironolactone will improve exercise tolerance and quality of life in elderly patients with isolated diastolic heart failure (DHF).

Condition	Intervention	Phase
Diastolic Heart Failure Heart Failure, Congestive	Drug: Spironolactone Drug: Placebo	Phase III

MedlinePlus related topics: Exercise and Physical Fitness Heart Failure

Drug Information available for: Spironolactone

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Exercise Intolerance in Elderly Diastolic Heart Failure

Further study details as provided by National Institute on Aging (NIA):

Primary Outcome Measures:

Exercise intolerance [ Time Frame: Baseline, 4 and 9 months ] [ Designated as safety issue: No ]
quality of life [ Time Frame: Baseline, 4 and 9 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Concentric left ventricular remodeling [ Time Frame: Baseline, 4 and 9 months ] [ Designated as safety issue: No ]
left ventricular diastolic stiffness [ Time Frame: Baseline, 4 and 9 months ] [ Designated as safety issue: No ]
serum markers of myocardial fibrosis, procollagen type III amino-terminal peptide (PIIINP) and collagen type I carboxy-terminal pro-peptide (CICP) [ Time Frame: Baseline, 4 and 9 months ] [ Designated as safety issue: No ]

Enrollment:	80
Study Start Date:	April 2005
Estimated Study Completion Date:	June 2008
Estimated Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Spironolactone	Drug: Spironolactone 25mg tablet daily for 9 months
2: Placebo Comparator Placebo	Drug: Placebo Placebo tablet daily for 9 months

Detailed Description:

Exercise intolerance due to diastolic heart failure (DHF) is a major cause of disability among older Americans. Several lines of evidence suggest that aldosterone antagonism may improve exercise tolerance in DHF. Spironolactone is a generic, inexpensive aldosterone antagonist. In an open-label pilot study of spironolactone in 10 elderly patients with isolated DHF there were significant improvements in exercise intolerance, quality of life, and left ventricular (LV) diastolic stiffness. Therefore, the primary aim of this study is to test the hypothesis that spironolactone will improve exercise tolerance and quality of life in elderly patients with isolated DHF. The secondary aim is to determine whether the improvements in exercise tolerance are related to improvements in abnormal concentric LV remodeling, LV diastolic stiffness, and myocardial fibrosis. These results will be important, not only because diastolic heart failure is highly prevalent among the elderly, but also because exercise intolerance is a pivotal outcome that is modifiable, is independent of mortality, and is a critical determinant of quality of life and disability among the elderly.

A total of 72 participants aged 60 or older will be randomized to receive either spironolactone 25mg daily or a placebo. There will be 9 visits over the 9-month trial period. Three testing visits will last approximately 2 hours each, and 6 follow-up visits will each last approximately 30 minutes.

Eligibility

Ages Eligible for Study:	60 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Ambulatory
Medically stable
Ages 60 or older
Diagnosis of diastolic heart failure

Exclusion Criteria:

Valvular heart disease
Significant change in cardiac medication within the past 4 weeks
Uncontrolled hypertension
Recent or debilitating stroke
Cancer or other noncardiovascular conditions with life expectancy less than 2 years
Anemia
Elevated serum potassium
Renal insufficiency
Psychiatric disease (uncontrolled major psychoses, depression, dementia, or personality disorder)
Allergy to spironolactone; currently taking spironolactone or any aldosterone antagonist
Plans to leave area within 1 year
Refuses informed consent
Failure to pass screening tests: pulmonary function, echocardiogram, or exercise
Contra-indications to magnetic resonance imaging [MRI] (indwelling metal-containing prosthesis; pacemaker or defibrillator; history of welding occupation; uncontrollable claustrophobia)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00123955

Locations

United States, North Carolina
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, United States, 27157

Sponsors and Collaborators

National Institute on Aging (NIA)

Investigators

Principal Investigator:

Dalane W. Kitzman, MD

Professor of Internal Medicine, Cardiology, Director of Echocardiography, Wake Forest University Health Sciences

More Information

Publications:

Kitzman DW, Little WC, Brubaker PH, Anderson RT, Hundley WG, Marburger CT, Brosnihan B, Morgan TM, Stewart KP. Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA. 2002 Nov 6;288(17):2144-50.

Kitzman DW, Higginbotham MB, Cobb FR, Sheikh KH, Sullivan MJ. Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism. J Am Coll Cardiol. 1991 Apr;17(5):1065-72.

Kitzman DW, Gardin JM, Gottdiener JS, Arnold A, Boineau R, Aurigemma G, Marino EK, Lyles M, Cushman M, Enright PL. Importance of heart failure with preserved systolic function in patients > or = 65 years of age. CHS Research Group. Cardiovascular Health Study. Am J Cardiol. 2001 Feb 15;87(4):413-9.

Zannad F, Alla F, Dousset B, Perez A, Pitt B. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators. Circulation. 2000 Nov 28;102(22):2700-6. Erratum in: Circulation 2001 Jan 23;103(3):476.

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.

Cicoira M, Zanolla L, Franceschini L, Rossi A, Golia G, Zeni P, Caruso B, Zardini P. Relation of aldosterone "escape" despite angiotensin-converting enzyme inhibitor administration to impaired exercise capacity in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2002 Feb 15;89(4):403-7.

Responsible Party:	Wake Forest University Health Science ( Dr. Dalane Kitzman )
Study ID Numbers:	AG0030, 2R01 AG018915-05
Study First Received:	July 22, 2005
Last Updated:	December 21, 2007
ClinicalTrials.gov Identifier:	NCT00123955
Health Authority:	United States: Federal Government

Study placed in the following topic categories:

Heart Failure, Diastolic
Heart Failure
Heart Diseases
Spironolactone

Additional relevant MeSH terms:

Aldosterone Antagonists
Natriuretic Agents
Therapeutic Uses
Hormone Antagonists
Physiological Effects of Drugs

Diuretics
Hormones, Hormone Substitutes, and Hormone Antagonists
Cardiovascular Diseases
Cardiovascular Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009