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
Protocol serial number	N/A
Sponsor	Georg-August University of Göttingen (Georg-August-Universität Göttingen) (Germany)
Funder	Federal Ministry for Education and Research (BMBF), Health Research (Germany)

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

Primary study design	Interventional
Study design	Multicenter, prospective, randomised, double-blinded, placebo-controlled, parallel group, phase IIb trial
Secondary study design	Randomised controlled trial
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
Phase	Phase II
Drug / device / biological / vaccine name(s)	Spironolactone
Primary outcome measure(s)	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
Key secondary outcome measure(s)	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)
Completion date	31/10/2008

Eligibility

Participant type(s)	Patient
Age group	Senior
Sex	All
Target sample size at registration	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

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	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?
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
Other publications	prototcol	01/08/2010		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.