PIE II: Pharmacological Intervention in the Elderly II

Heart Failure, Congestive Clinical Trial

Official title:

Exercise Intolerance in Elderly Diastolic Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00123955
• Other study ID #: AG0030
• Secondary ID: R01AG0189152R01A
• Status: Completed
• Phase: Phase 3
• Start date: April 2005
• Est. completion date: December 2012

Study information

• Verified date: February 2019
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: December 2012
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Diastolic Heart Failure
• Heart Failure
• Heart Failure, Congestive
• Heart Failure, Diastolic

Intervention

Drug:
• Spironolactone
25mg tablet daily for 9 months
• Placebo
Placebo tablet daily for 9 months

Locations

Country	Name	City	State
United States	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. Erratum in: Circulation 2001 Jan 23;103(3):476. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exercise Intolerance	Peak exercise VO2	Baseline, 4 and 9 months
Primary	Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire-total Score	The Minnesota Living with Heart Failure Questionnaire (MLHF) is a self-administered disease-specific questionnaire for patients with Heart Failure, comprising 21 items rated on six-point Likert scales, representing different degrees of impact of HF on HRQoL, from 0 (none) to 5 (very much). It provides a total score (range 0-105, from best to worst HRQoL), as well as scores for two dimensions, physical (8 items, range 0-40) and emotional (5 items, range 0-25). The other eight items (of the total of 21) are only considered for the calculation of the total score.; Scale of 0-105:The higher the score the worse the heart failure related Quality of Life.	Baseline, 4 and 9 months
Secondary	Concentric Left Ventricular Remodeling	Left ventricle measurements by MRI: Mass/end diastolic volume ratio: g/ml	Baseline, 9 month
Secondary	Left Ventricular Diastolic Stiffness	Echocardiography Doppler measurement of left ventricular diastolic function: Early mitral annulus velocity (lateral) (Ea; cm/s)	Baseline, 4 month and 9 month