Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Acronym
Aldo-DHF
Study hypothesis
The primary objective of this study is to determine in subjects with diastolic heart failure whether spironolactone is superior to placebo in improving maximal exercise capacity and diastolic heart function. Secondary objectives of this study are to determine in subjects with diastolic heart failure whether spironolactone is superior to placebo in improving several other measures of exercise capacity and diastolic function, as well as quality of life, neuroendocrine activation, morbidity and mortality. The study will also investigate clinical safety aspects.
Ethics approval
Local ethics committee in Göttingen and the BfAM.
Study design
Multicenter, prospective, randomised, double-blinded, placebo-controlled, parallel group, phase IIb trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Diastolic heart failure
Intervention
Once randomised, all patients will take study medication (25 mg spironolactone or placebo) once daily in the morning for 12 months. Patients recruited in the first six months will be followed up to 18 months. Spironolactone will be applied in one fixed dose, i.e., 25 mg, but may be down titrated if indicated.
Intervention type
Drug
Phase
Phase II
Drug names
Spironolactone
Primary outcome measures
1. Change in maximum exercise capacity (peak VO2 on spiroergometry) at 12 months compared to baseline
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
1. Change in primary endpoints at 18 months
2. Change in the echocardiographic Grade of diastolic dysfunction
3. Change in neuroendocrine activation (natriuretic peptides)
4. Change in six minutes walking distance
5. Change in quality of life (Minnesota living with heart failure questionnaire; Short Form Health Survey [SF-36])
6. Combined and separately morbidity and mortality (all-cause; cardiovascular)
Overall trial start date
01/11/2006
Overall trial end date
31/10/2008
Reason abandoned
Eligibility
Participant 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
Participant type
Patient
Age group
Senior
Gender
Both
Target number of participants
420
Participant 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
Recruitment start date
01/11/2006
Recruitment end date
31/10/2008
Locations
Countries of recruitment
Germany
Trial participating centre
Department of Cardiology and Pneumology
Göttingen
37075
Germany
Sponsor information
Organisation
Georg-August University of Göttingen (Georg-August-Universität Göttingen) (Germany)
Sponsor details
c/o Prof. Dr. Burkert Pieske
Robert-Koch-Str. 40
Göttingen
37075
Germany
+49 (0)551 398925
pieske@med.uni-goettingen.de
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
Federal Ministry for Education and Research (BMBF), Health Research (Germany)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
1. 2010 prototcol in: http://www.ncbi.nlm.nih.gov/pubmed/20538867
2. 2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23443441
3. 2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/24182675
Publication citations
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Results
Edelmann F, Wachter R, Schmidt AG, Kraigher-Krainer E, Colantonio C, Kamke W, Duvinage A, Stahrenberg R, Durstewitz K, Löffler M, Düngen HD, Tschöpe C, Herrmann-Lingen C, Halle M, Hasenfuss G, Gelbrich G, Pieske B, , Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial., JAMA, 2013, 309, 8, 781-791, doi: 10.1001/jama.2013.905.
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Results
Edelmann F, Gelbrich G, Duvinage A, Stahrenberg R, Behrens A, Prettin C, Kraigher-Krainer E, Schmidt AG, Düngen HD, Kamke W, Tschöpe C, Herrmann-Lingen C, Halle M, Hasenfuss G, Wachter R, Pieske B, Differential interaction of clinical characteristics with key functional parameters in heart failure with preserved ejection fraction - results of the Aldo-DHF trial., Int. J. Cardiol., 2013, 169, 6, 408-417, doi: 10.1016/j.ijcard.2013.10.018.
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Edelmann F, Schmidt AG, Gelbrich G, Binder L, Herrmann-Lingen C, Halle M, Hasenfuss G, Wachter R, Pieske B, Rationale and design of the 'aldosterone receptor blockade in diastolic heart failure' trial: a double-blind, randomized, placebo-controlled, parallel group study to determine the effects of spironolactone on exercise capacity and diastolic function in patients with symptomatic diastolic heart failure (Aldo-DHF)., Eur. J. Heart Fail., 2010, 12, 8, 874-882, doi: 10.1093/eurjhf/hfq087.