Effects of selective serotonin re-uptake inhibition on MOrbidity, mOrtality and mood in Depressed Heart Failure patients
| ISRCTN | ISRCTN33128015 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN33128015 |
| Secondary identifying numbers | N/A |
- Submission date
- 22/01/2007
- Registration date
- 10/05/2007
- Last edited
- 04/07/2016
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Mental and Behavioural Disorders
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
Contact information
Scientific
University of Wuerzburg
Comprehensive Heart Failure Center (CHFC)
Straubmühlweg 2a, Haus A9
Wuerzburg
97078
Germany
| Phone | +49 (0)931 201 46361 |
|---|---|
| angermann_c@ukw.de |
Study information
| 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 |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Effects of selective serotonin re-uptake inhibition on MOrbidity, mOrtality and mood in Depressed Heart Failure patients |
| Study 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(s) | 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 |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Escitalopram |
| Primary outcome measure | 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 study start date | 01/08/2007 |
| Overall study end date | 31/08/2014 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 414 (depending on number of endpoints reached) |
| 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 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
Study participating centre
97078
Germany
Sponsor information
Government
c/o Dr Isabell Hahn
Heinrich-Konen-Str. 1
Bonn
53227
Germany
| Phone | +49 (0)228 3821 119 |
|---|---|
| Isabell.Hahn@dlr.de | |
| Website | http://www.bmbf.de/ |
"ROR" |
https://ror.org/04pz7b180 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- Federal Ministry of Education and Research, BMBF
- Location
- Germany
Results and Publications
| Intention to publish date | |
|---|---|
| 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 |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 01/12/2007 | Yes | No | |
| Results article | results | 28/06/2016 | Yes | No |
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).
