Diastolic Heart Failure, Heart Failure, Congestive
Conditions
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.
Interventions
DRUGSpironolactone
25mg tablet daily for 9 months
DRUGPlacebo
Placebo tablet daily for 9 months
Sponsors
National Institute on Aging (NIA)
Wake Forest University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exercise Intolerance | Baseline, 4 and 9 months | Peak exercise VO2 |
| Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire-total Score | Baseline, 4 and 9 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentric Left Ventricular Remodeling | Baseline, 9 month | Left ventricle measurements by MRI: Mass/end diastolic volume ratio: g/ml |
| Left Ventricular Diastolic Stiffness | Baseline, 4 month and 9 month | Echocardiography Doppler measurement of left ventricular diastolic function: Early mitral annulus velocity (lateral) (Ea; cm/s) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Spironolactone Spironolactone
Spironolactone: 25mg tablet daily for 9 months | 42 |
| Placebo Placebo
Placebo: Placebo tablet daily for 9 months | 38 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 3 |
Baseline characteristics
| Characteristic | Total | Spironolactone | Placebo |
|---|---|---|---|
| Age, Continuous | 70.8 years STANDARD_DEVIATION 7.3 | 70.0 years STANDARD_DEVIATION 7.3 | 71.7 years STANDARD_DEVIATION 7.3 |
| Peak VO2 (ml/kg/min) | 13.4 ml/kg/min STANDARD_DEVIATION 2.9 | 13.5 ml/kg/min STANDARD_DEVIATION 2.9 | 13.3 ml/kg/min STANDARD_DEVIATION 2.9 |
| Sex: Female, Male Female | 64 Participants | 34 Participants | 30 Participants |
| Sex: Female, Male Male | 16 Participants | 8 Participants | 8 Participants |
| Workload (Watts) | 62 Watts STANDARD_DEVIATION 26 | 63 Watts STANDARD_DEVIATION 26 | 60 Watts STANDARD_DEVIATION 26 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 42 | 0 / 38 |
| serious Total, serious adverse events | 6 / 42 | 6 / 38 |
Outcome results
Primary
Exercise Intolerance
Peak exercise VO2
Time frame: Baseline, 4 and 9 months
Population: The outcome measure data uses data from all participants with 4 and/or 9 month follow-up. Thirty-seven participants randomized to spironolactone and 35 participants randomized to placebo completed 4 months of follow-up, and 37 participants randomized to spironolactone and 34 participants randomized to placebo completed 9 months of follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Spironolactone | Exercise Intolerance | Baseline | 13.5 ml/kg/min | Standard Deviation 2.9 |
| Spironolactone | Exercise Intolerance | 4 months | 13.6 ml/kg/min | Standard Deviation 3.5 |
| Spironolactone | Exercise Intolerance | 9 months | 13.8 ml/kg/min | Standard Deviation 3.2 |
| Placebo | Exercise Intolerance | Baseline | 13.3 ml/kg/min | Standard Deviation 2.9 |
| Placebo | Exercise Intolerance | 4 months | 13.5 ml/kg/min | Standard Deviation 3.4 |
| Placebo | Exercise Intolerance | 9 months | 13.9 ml/kg/min | Standard Deviation 3.7 |
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.
Time frame: Baseline, 4 and 9 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Spironolactone | Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire-total Score | Baseline | 32 units on a scale | Standard Deviation 21 |
| Spironolactone | Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire-total Score | 4 months | 29 units on a scale | Standard Deviation 20 |
| Spironolactone | Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire-total Score | Final- 9 months | 29 units on a scale | Standard Deviation 18 |
| Placebo | Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire-total Score | Baseline | 28 units on a scale | Standard Deviation 19 |
| Placebo | Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire-total Score | 4 months | 29 units on a scale | Standard Deviation 23 |
| Placebo | Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire-total Score | Final- 9 months | 25 units on a scale | Standard Deviation 18 |
Secondary
Concentric Left Ventricular Remodeling
Left ventricle measurements by MRI: Mass/end diastolic volume ratio: g/ml
Time frame: Baseline, 9 month
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Spironolactone | Concentric Left Ventricular Remodeling | baseline | 1.8 g/ml | Standard Deviation 0.4 |
| Spironolactone | Concentric Left Ventricular Remodeling | 9 month | 1.7 g/ml | Standard Deviation 0.4 |
| Placebo | Concentric Left Ventricular Remodeling | baseline | 1.7 g/ml | Standard Deviation 0.5 |
| Placebo | Concentric Left Ventricular Remodeling | 9 month | 1.6 g/ml | Standard Deviation 0.4 |
Secondary
Left Ventricular Diastolic Stiffness
Echocardiography Doppler measurement of left ventricular diastolic function: Early mitral annulus velocity (lateral) (Ea; cm/s)
Time frame: Baseline, 4 month and 9 month
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Spironolactone | Left Ventricular Diastolic Stiffness | baseline | 7.0 cm/s | Standard Deviation 2.1 |
| Spironolactone | Left Ventricular Diastolic Stiffness | 4 month | 7.0 cm/s | Standard Deviation 2.1 |
| Spironolactone | Left Ventricular Diastolic Stiffness | 9 month | 7.4 cm/s | Standard Deviation 2.2 |
| Placebo | Left Ventricular Diastolic Stiffness | baseline | 6.8 cm/s | Standard Deviation 1.4 |
| Placebo | Left Ventricular Diastolic Stiffness | 4 month | 6.8 cm/s | Standard Deviation 1.4 |
| Placebo | Left Ventricular Diastolic Stiffness | 9 month | 6.6 cm/s | Standard Deviation 1.6 |