Condition category
Mental and Behavioural Disorders
Date applied
22/01/2007
Date assigned
10/05/2007
Last edited
04/07/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Depression and chronic heart failure (CHF) are frequent and often occur together. Major depression affects 20-40% of CHF patients and impacts adversely on quality of life, clinical outcomes and healthcare costs. Some antidepressants, such as escitalopram, act via increasing the amount of serotonin in the brain. Currently, it is uncertain whether treatment with such antidepressants improves depression and outcomes in CHF patients, and, if yes, by which mechanisms. Therefore, this study aims to investigate the effects of escitalopram on morbidity, mortality and mood in depressed CHF patients over a prolonged period of time.

Who can participate?
Patients aged 18 or over who suffer from chronic systolic heart failure and major depression.

What does the study involve?
Patients are randomly allocated to one of two possible treatments (either escitalopram or placebo [dummy] tablets) and receive at the same time optimal cardiological treatment, as the dose of the study drug is increased over a period of 3 months. During that time, specialized nurses perform support and monitoring via telephone, thus closely supervising treatment effects and patients’ health and mood status. After 3 months, nurse monitoring is decreased to bimonthly telephone calls. During follow-up mood is also closely supervised by psychologists and psychiatrists, who intervene in case of significant worsening. During the total 24-month study period patients undergo nine study visits.

What are the possible benefits and risks of participating?
There are no risks or disadvantages to participate in the trial which exceed the described and known side effects of escitalopram. It is not known whether one or the other treatment strategy (escitalopram or placebo treatment) is superior for patients with chronic heart failure. Furthermore, all participants will receive an optimized treatment plan regarding the management of heart failure.

Where is the study run from?
University of Wuerzburg (Germany)

When is the study starting and how long is it expected to run for?
The study started in 2009 and will be completed in 2014

Who is funding the study?
The study is supported by the German Ministry of Education and Research. Lundbeck GmbH provides study medication and additional financial support for patient screening.

Who is the main contact?
Prof. Dr. C. E. Angermann
angermann_c@ukw.de

Trial website

http://www.chfc.ukw.de/en/information-for-physicians/clinical-trials/mood-hf.html

Contact information

Type

Scientific

Primary contact

Prof Christiane Angermann

ORCID ID

Contact details

University of Wuerzburg
Comprehensive Heart Failure Center (CHFC)
Straubmühlweg 2a
Haus A9
Wuerzburg
97078
Germany
+49 (0)931 201 46361
angermann_c@ukw.de

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Effects of selective serotonin re-uptake inhibition on MOrbidity, mOrtality and mood in Depressed Heart Failure patients

Acronym

MOOD-HF

Study hypothesis

To investigate the effects of treatment with the selective serotonin re-uptake inhibitor escitalopram compared to placebo on morbidity and mortality in chronic heart failure patients with a current episode of major depression.

Protocol can be found at: http://www.chfc.ukw.de/fileadmin/uk/chfc/Dokumente/Studien_Flyer/MOOD-HF_Pruefplan.pdf

Ethics approval

Ethics Committee of the Medical Faculty of the University of Würzburg, primary approval: 27/05/2008, amendment 01: 06/02/2009, amendment 02: 14/10/2009, amendment 03: 06/08/2010, amendment 04: 08/12/2010, amendment 05: 02/03/2011, amendment 06: 30/06/2011, amendment 07: 30/09/2011, amendment 08: 06/08/2012, amendment 09: 10/12/2012, amendment 10: 17/06/2013, amendment 11: 24/03/2014

Study design

Prospective randomised double-blind placebo-controlled two-armed parallel-group multicentre phase IV trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Heart failure and co-morbid depression

Intervention

Current interventions as of 15/04/2014:
1. Experimental intervention: nurse support and cardiological care and escitalopram 10 to 20 mg/day orally (p.o.)
2. Control intervention: nurse support and cardiological care and placebo 10 to 20 mg/day p.o.

Duration of intervention per patient: minimum 6 months, maximum 24 months, down titration 1 month.

Previous interventions:
1. Experimental intervention: cardiological care and escitalopram 10 to 20 mg/day orally (p.o.)
2. Control intervention: cardiological care and placebo 10 to 20 mg/day p.o.

Duration of intervention per patient: minimum 12 months, maximum 24 months, down titration 1 months.

Intervention type

Drug

Phase

Phase IV

Drug names

Escitalopram

Primary outcome measures

Time to first event of death or hospitalisation.

Secondary outcome measures

Major secondary outcome:
Reduction of the degree of depression as assessed by the Patient Health Questionnaire (PHQ-9) Scale and the Montgomery Asberg Depression Scale (MADRS)

Further secondary outcomes:
1. Days alive out of hospital
2. PHQ-GAD-7 (General Anxiety Disorder) scale
3. Quality of life as assessed by the 36-item Short Form Health Survey (SF-36), and the Kansas City Cardiomyopathy Questionnaire (KCCQ)
4. Cardiovascular mortality
5. Cardiovascular morbidity
6. Health economy
7. Adherence to HF and study medication
8. CHF severity
9. Parameters of inflammation
10. Sympathetic nervous system function
11. Escitalopram plasma levels
12. Platelet function/coagulation (substudy)
13. Vasoreactivity (substudy)

Overall trial start date

01/08/2007

Overall trial end date

31/08/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged more than 18 years
2. Stable systolic chronic heart failure (CHF) (New York Heart Association [NYHA] II to IV) with left ventricular ejection fraction (LVEF) less than 45%
3. Current comorbid episode of major depression confirmed by Structured Clinical Interview for Diagnostic and Statistical Manual for mental disorders - fourth edition (DSM-IV) (SCID)
4. Written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

414 (depending on number of endpoints reached)

Participant exclusion criteria

Current inclusion criteria as of 15/04/2014:
1. Current treatment with a selective serotonin re-uptake inhibitor (SSRI)
2. Previous treatment failure with escitalopram
3. Acute myocardial infarction (less than three months), acute cardiac decompensation, recent (less than three months) or planned (less than 12 months) cardiac surgery
4. Advanced renal failure (Modification of Diet in Renal Disease [MDRD] less than 30 ml/min)
5. Thyreotoxicosis
6. Reduced life expectancy due to other co-morbidity (e.g. malignancy)
7. Moderate or severe hepatic insufficiency (plasma levels of hepatic enzymes more than threefold of the upper level of the normal range)
8. Known evidence of major psychiatric comorbidity:
8.1. Imminent risk for or history of attempted suicide
8.2. Schizophrenia and spectrum disorders
8.3. Bipolar affective disorder
8.4. Current substance disorder
8.5. Moderate and severe Dementia
8.6. Severe depressive episode with psychotic features
9. Other contraindications against therapy with escitalopram (according to product information)
10. Participation in another clinical trial
11. Inability to comply with PHQ-9 and/or SCID testing and/or telephone monitoring for mental or linguistic reasons or lack of access to telephone
12. Pregnancy or nursing period
13. Women with child bearing potential without effective contraception during the conduct of the trial
14. Expected low compliance with the visit schedule or telephone monitoring (e.g., due to comorbidity or travel distance to the trial site)
15. Patients with normal ventricular activation (no bundle branch block (total or incomplete), no other intraventricular conduction delay and no pacemaker) and known QTc* prolongation ≥ 500 ms OR inborn long QT syndrome
16. Patients with current treatment with drugs inducing QT prolongation, such as antiarrhythmic drugs class IA and III, anti-psychotics, tricyclic antidepressants

Previous inclusion criteria:
1. Current treatment with a selective serotonin re-uptake inhibitor (SSRI)
2. Previous treatment failure with escitalopram
3. Acute myocardial infarction (less than 3 months), acute cardiac decompensation, recent (less than 3 months) or planned (less than 12 months) cardiac surgery
4. Advanced renal failure (Modification of Diet in Renal Disease [MDRD] less than 30 ml/min)
5. Thyreotoxicosis
6. Reduced life expectancy due to other co-morbidity (e.g. malignancy)
7. Moderate or severe hepatic insufficiency (plasma levels of hepatic enzymes more than threefold of the upper level of the normal range)
8. Known evidence of major psychiatric comorbidity:
8.1. Imminent risk for or history of attempted suicide
8.2. Schizophrenia and spectrum disorders
8.3. Bipolar affective disorder
8.4. Current substance disorder
8.5. Dementia
8.6. Severe depressive episode with psychotic features
8.7. Delirium
9. Other contraindications against therapy with escitalopram (according to product information)

Recruitment start date

01/08/2007

Recruitment end date

31/08/2014

Locations

Countries of recruitment

Germany

Trial participating centre

University of Wuerzburg
Wuerzburg
97078
Germany

Sponsor information

Organisation

German Federal Ministry of Education and Research (Bundesministerium Für Bildung und Forschung [BMBF]) (Germany)

Sponsor details

c/o Dr Isabell Hahn
Heinrich-Konen-Str. 1
Bonn
53227
Germany
+49 (0)228 3821 119
Isabell.Hahn@dlr.de

Sponsor type

Government

Website

http://www.bmbf.de/

Funders

Funder type

Government

Funder name

Bundesministerium für Bildung und Forschung

Alternative name(s)

Federal Ministry of Education and Research, BMBF

Funding Body Type

government organisation

Funding Body Subtype

federal

Location

Germany

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

2007 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/18029292
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/27367876

Publication citations

  1. Protocol

    Angermann CE, Gelbrich G, Störk S, Fallgatter A, Deckert J, Faller H, Ertl G, , Rationale and design of a randomised, controlled, multicenter trial investigating the effects of selective serotonin re-uptake inhibition on morbidity, mortality and mood in depressed heart failure patients (MOOD-HF)., Eur. J. Heart Fail., 2007, 9, 12, 1212-1222, doi: 10.1016/j.ejheart.2007.10.005.

  2. Results

    Angermann CE, Gelbrich G, Störk S, Gunold H, Edelmann F, Wachter R, Schunkert H, Graf T, Kindermann I, Haass M, Blankenberg S, Pankuweit S, Prettin C, Gottwik M, Böhm M, Faller H, Deckert J, Ertl G; MOOD-HF Study Investigators and Committee Members, Effect of Escitalopram on All-Cause Mortality and Hospitalization in Patients With Heart Failure and Depression: The MOOD-HF Randomized Clinical Trial, JAMA, 2016 , 315, 24, 2683-2693, doi: 10.1001/jama.2016.7635.

Additional files

Editorial Notes

04/07/2016: Publication reference added. 15/04/2014: the following changes were made to the trial record: 1. The overall trial end date was changed from 30/09/2010 to 31/08/2014. 2. The target number of participants was changed from 700 to 414 (depending on number of endpoints reached).