PIE II: Pharmacological Intervention in the Elderly II

Study Overview
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Brief Summary
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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
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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.

Official Title
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Exercise Intolerance in Elderly Diastolic Heart Failure

Conditions
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Diastolic Heart Failure, Heart Failure, Congestive

Intervention / Treatment
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* Drug: Spironolactone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Spironolactone | Drug: Spironolactone<br>* 25mg tablet daily for 9 months<br>* Other names: Aldactone;|
| Placebo Comparator: 2<br>Placebo | Drug: Placebo<br>* Placebo tablet daily for 9 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise Intolerance | Peak exercise VO2 | Baseline, 4 and 9 months | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentric Left Ventricular Remodeling | Left ventricle measurements by MRI: Mass/end diastolic volume ratio: g/ml | Baseline, 9 month | 
| 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 |