Clinical trial NCT00123955: PIE II: Pharmacological Intervention in the Elderly II
Official title: Exercise Intolerance in Elderly Diastolic Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diastolic Heart Failure
Heart Failure, Congestive
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2005-07-26
Enrollment: 80
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to examine whether spironolactone will improve exercise tolerance and quality of life in elderly patients with heart failure preserved ejection fraction (HFPEF).

Detailed description: Exercise intolerance due to HFPEF is a major cause of disability among older Americans. Several lines of evidence suggest that aldosterone antagonism may improve exercise tolerance in HFPEF. 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 HFPEF. A total of 72 participants aged 60 or older will be randomized to receive either spironolactone 25mg daily or a placebo.

Eligibility 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)

Primary outcomes:
measure: Exercise Intolerance
timeFrame: Baseline, 4 and 9 months
measure: Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire-total Score
timeFrame: Baseline, 4 and 9 months
Secondary outcomes:
measure: Concentric Left Ventricular Remodeling
timeFrame: Baseline, 9 month
measure: Left Ventricular Diastolic Stiffness
timeFrame: Baseline, 4 month and 9 month
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
Study officials:
affiliation: Professor of Internal Medicine, Cardiology, Director of Echocardiography, Wake Forest University Health Sciences
name: Dalane W. Kitzman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1001/jama.288.17.2144.
citation: 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. doi: 10.1016/0735-1097(91)90832-t.
citation: Kitzman DW, Gardin JM, Gottdiener JS, Arnold A, Boineau R, Aurigemma G, Marino EK, Lyles M, Cushman M, Enright PL; Cardiovascular Health Study Research Group. 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. doi: 10.1016/s0002-9149(00)01393-x.
citation: 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. doi: 10.1161/01.cir.102.22.2700.
citation: 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. doi: 10.1056/NEJM199909023411001.
citation: 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. doi: 10.1016/s0002-9149(01)02261-5.
citation: Kitzman DW, Herrington DM, Brubaker PH, Moore JB, Eggebeen J, Haykowsky MJ. Carotid arterial stiffness and its relationship to exercise intolerance in older patients with heart failure and preserved ejection fraction. Hypertension. 2013 Jan;61(1):112-9. doi: 10.1161/HYPERTENSIONAHA.111.00163. Epub 2012 Nov 12.
citation: Daniel KR, Wells G, Stewart K, Moore B, Kitzman DW. Effect of aldosterone antagonism on exercise tolerance, Doppler diastolic function, and quality of life in older women with diastolic heart failure. Congest Heart Fail. 2009 Mar-Apr;15(2):68-74. doi: 10.1111/j.1751-7133.2009.00056.x.