Aldosterone receptor blockade in Diastolic Heart Failure: a double-blind, randomised, placebo-controlled, parallel group study to determine the effects of spironolactone on exercise capacity and diastolic function in patients with symptomatic diastolic heart failure

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 422

Inclusion Criteria

1. Current heart failure symptoms consistent with New York Heart Association (NYHA) grade II or beyond
2. Left Ventricular Ejection Fraction (LVEF) more than or equal to 50% at rest
3. Sinus rhythm
4. Echocardiographic parameters of diastolic dysfunction (more than or equal to Grade I)
5. Peak Oxygen uptake (VO2) less than or equal to 20 ml/kg/min
6. Males and females of age 50 years or over
7. Written informed consent of the patient

Exclusion Criteria

1. Definite or probable pulmonary disease (Vital Capacity [VC] less than 80% or Forced Expiratory Volume in one second [FEV1] less than 80% of reference values on spirometry)
2. Severe obesity (Body Mass Index [BMI] more than or equal to 36 kg/m^2)
3. Psychological disorders with suspected interaction to study outcome
4. Prior documented intolerance to an aldosterone receptor antagonist
5. Prior documented systolic heart failure (LVEF less than or equal to 40%)
6. Changes in concomitant medication within the last two weeks prior screening visit
7. Significant coronary artery disease (current angina pectoris or ischemia on stress tests; untreated coronary stenosis more than 50%; Myocardial infarction or Coronary Artery Bypass Graft (CAGB) within the last three months)
8. Known contraindications for spironolactone
9. Significant laboratory abnormalities (potassium more than or equal to 5.1 mmol/L; haemoglobin less than or equal to 11g/dL, hematocrit less than or equal to 33%)
10. Significant renal dysfunction (creatinine more than 1.8 mg/dL)
11. Concomitant therapy with a potassium-sparing diuretic (e.g., triamterene, amiloride), potassium substitution, or high-dose acetylsalicylic acid (more than 500 mg/d) or permanent intake of non-steroidal antiphlogistic agents, digitalis
12. Insulin-dependent diabetes mellitus with a history of ketoacidosis
13. Suspected metabolic acidosis
14. Significant hypotension (blood pressure less than 90 mmHg systolic and/or less than 50 mmHg diastolic)
15. Any patient characteristic that may interfere with compliance with the study protocol, such as dementia, substance abuse, history of non-compliance with prescribed medications or medical appointments
16. Pregnant or nursing women
17. Women with child bearing potency without effective contraception (except for implants, injectables, combined oral contraceptives, some IntraUterine Devices [IUDs] or vasectomised partner)
18. Concomitant participation in other clinical trials
19. Therapy with an aldosterone receptor antagonist within the last three months
20. Participation in another clinical trial within the last 30 days

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Change in maximum exercise capacity (peak VO2 on spiroergometry) at 12 months compared to baseline<br>2. Change in E/E´ (relation peak early transmitral ventricular filling velocity/early diastolic tissue Doppler velocity) as indicator of Left Ventricular End Diastolic Pressure (LVEDP) at 12 months

Secondary Outcome Measures

Name	Time	Method
1. Change in primary endpoints at 18 months <br>2. Change in the echocardiographic Grade of diastolic dysfunction <br>3. Change in neuroendocrine activation (natriuretic peptides)<br>4. Change in six minutes walking distance<br>5. Change in quality of life (Minnesota living with heart failure questionnaire; Short Form Health Survey [SF-36])<br>6. Combined and separately morbidity and mortality (all-cause; cardiovascular)

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