Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Burkert Pieske

ORCID ID

Contact details

Department of Cardiology and Pneumology
Georg-August-Universität Göttingen
Robert-Koch-Str. 40
Göttingen
37075
Germany
+49 (0)551-398925

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

http://www.uni-goettingen.de/

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

  1. 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.

  2. 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.

  3. 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.

Editorial Notes