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
ISRCTN | ISRCTN94726526 |
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DOI | https://doi.org/10.1186/ISRCTN94726526 |
Secondary identifying numbers | N/A |
- Submission date
- 10/10/2006
- Registration date
- 07/11/2006
- Last edited
- 06/04/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Prof Burkert Pieske
Scientific
Scientific
Department of Cardiology and Pneumology
Georg-August-Universität Göttingen
Robert-Koch-Str. 40
Göttingen
37075
Germany
Phone | +49 (0)551-398925 |
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pieske@med.uni-goettingen.de |
Study information
Study design | Multicenter, prospective, randomised, double-blinded, placebo-controlled, parallel group, phase IIb trial |
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Primary study design | Interventional |
Secondary study design | Randomised controlled trial |
Study setting(s) | Not specified |
Study type | Treatment |
Scientific title | 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 |
Study acronym | Aldo-DHF |
Study objectives | 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(s) | Local ethics committee in Göttingen and the BfAM. |
Health condition(s) or problem(s) studied | 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 |
Pharmaceutical study type(s) | |
Phase | Phase II |
Drug / device / biological / vaccine name(s) | Spironolactone |
Primary outcome measure | 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 study start date | 01/11/2006 |
Completion date | 31/10/2008 |
Eligibility
Participant type(s) | Patient |
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Age group | Senior |
Sex | Both |
Target number of participants | 420 |
Total final enrolment | 422 |
Key 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 |
Key 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 |
Date of first enrolment | 01/11/2006 |
Date of final enrolment | 31/10/2008 |
Locations
Countries of recruitment
- Germany
Study participating centre
Department of Cardiology and Pneumology
Göttingen
37075
Germany
37075
Germany
Sponsor information
Georg-August University of Göttingen (Georg-August-Universität Göttingen) (Germany)
University/education
University/education
c/o Prof. Dr. Burkert Pieske
Robert-Koch-Str. 40
Göttingen
37075
Germany
Phone | +49 (0)551 398925 |
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pieske@med.uni-goettingen.de | |
Website | http://www.uni-goettingen.de/ |
https://ror.org/01y9bpm73 |
Funders
Funder type
Government
Federal Ministry for Education and Research (BMBF), Health Research (Germany)
No information available
Results and Publications
Intention to publish date | |
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Individual participant data (IPD) Intention to share | No |
IPD sharing plan summary | Not provided at time of registration |
Publication and dissemination plan | Not provided at time of registration |
IPD sharing plan | Not provided at time of registration |
Study outputs
Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
---|---|---|---|---|---|
Other publications | prototcol | 01/08/2010 | Yes | No | |
Results article | results | 27/02/2013 | Yes | No | |
Results article | results | 30/11/2013 | Yes | No | |
Results article | 19/10/2021 | 15/12/2021 | Yes | No | |
Results article | Post hoc analysis | 04/09/2021 | 22/03/2022 | Yes | No |
Results article | 05/04/2023 | 06/04/2023 | Yes | No |
Editorial Notes
06/04/2023: Publication reference added.
22/03/2022: Publication reference added.
15/12/2021: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the 2013 reference.