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
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

Department of Cardiology and Pneumology
Georg-August-Universität Göttingen
Robert-Koch-Str. 40
Göttingen
37075
Germany

Phone +49 (0)551-398925
Email pieske@med.uni-goettingen.de

Study information

Study designMulticenter, prospective, randomised, double-blinded, placebo-controlled, parallel group, phase IIb trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typeTreatment
Scientific titleAldosterone 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 acronymAldo-DHF
Study objectivesThe 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) studiedDiastolic heart failure
InterventionOnce 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 typeDrug
Pharmaceutical study type(s)
PhasePhase II
Drug / device / biological / vaccine name(s)Spironolactone
Primary outcome measure1. 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 measures1. 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 date01/11/2006
Completion date31/10/2008

Eligibility

Participant type(s)Patient
Age groupSenior
SexBoth
Target number of participants420
Total final enrolment422
Key inclusion criteria1. 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 criteria1. 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 enrolment01/11/2006
Date of final enrolment31/10/2008

Locations

Countries of recruitment

  • Germany

Study participating centre

Department of Cardiology and Pneumology
Göttingen
37075
Germany

Sponsor information

Georg-August University of Göttingen (Georg-August-Universität Göttingen) (Germany)
University/education

c/o Prof. Dr. Burkert Pieske
Robert-Koch-Str. 40
Göttingen
37075
Germany

Phone +49 (0)551 398925
Email pieske@med.uni-goettingen.de
Website http://www.uni-goettingen.de/
ROR logo "ROR" 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
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing planNot 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.