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Trial registered on ANZCTR


Registration number
ACTRN12610000223033
Ethics application status
Approved
Date submitted
3/03/2010
Date registered
17/03/2010
Date last updated
10/07/2019
Date data sharing statement initially provided
10/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Pharmacological Restoration of mOod in HEART Failure: PRO-HEART
Scientific title
A Double-blind, Randomized, Placebo-controlled, Parallel Group, Multi-centre Study to Assess the Efficacy of Escitalopram in the Treatment of Depression in Patients with Chronic Systolic Heart Failure
Secondary ID [1] 1469 0
None
Universal Trial Number (UTN)
Trial acronym
PRO-HEART
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 252217 0
Chronic systolic heart failure 252218 0
Condition category
Condition code
Mental Health 252403 252403 0 0
Depression
Cardiovascular 252404 252404 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Six months of blinded treatment with oral escitalopram titrated from 5 mg to 20mg daily and maintained at maximum tolerated dose. Participants in the treatment group who have improved to remission by 6 months will be provided with open-label maintenance therapy to 12 months.
Intervention code [1] 241560 0
Treatment: Drugs
Comparator / control treatment
Cellulose (oral tablet identical to escitalopram only without the active ingredient escitalopram oxalate and without the inactive ingredients purified talc, croscarmellose sodium and sodium hydroxide) taken daily for 6 months
Control group
Placebo

Outcomes
Primary outcome [1] 253279 0
Combined Major and Minor Depression:
Change in Cardiac Depression Scale (CDS) score
Timepoint [1] 253279 0
6 months from randomisation
Primary outcome [2] 253280 0
Combined Major and Minor Depression:
Change in 17 item GRID Hamilton Depression (HAM-D-17) Score
Timepoint [2] 253280 0
6 months from randomisation
Secondary outcome [1] 262280 0
Change in minor depression on Cardiac Depression Scale
Timepoint [1] 262280 0
6 months from randomisation
Secondary outcome [2] 262281 0
Change in major depression on Cardiac Depression scale
Timepoint [2] 262281 0
6 months from randomisation
Secondary outcome [3] 262282 0
Change in major depression on HAM-D-17 scores
Timepoint [3] 262282 0
6 months from randomisation
Secondary outcome [4] 262283 0
Change in any depression on Beck Depression Inventory
Timepoint [4] 262283 0
6 months from randomisation
Secondary outcome [5] 262284 0
Change in any depression on Hospital Anxiety and Depression Scale (HADS)
Timepoint [5] 262284 0
6 months from randomisation
Secondary outcome [6] 262285 0
Change in autonomic function as measured using heart rate variability (HRV)
Timepoint [6] 262285 0
6 months from randomisation
Secondary outcome [7] 262287 0
Change in pro-inflammatory cytokines as measured by commercial automated chemiluminescent Enzyme Immuno Assays (EIA) using an Immulite Analyser from Diagnostic Products Corporation, Los Angeles, Ca USA.
1. Tumor Necrosis Factor ? (TNF?). This is a competitive immunoassay using Alkaline Phosphatase labelled TNF? as tracer and adamantyl dioxetane as luminescent substrate for ALP enzyme.
2. Interleukin 6 (IL 6): a solid-phase, two-site chemiluminescent immunometric assay.
Timepoint [7] 262287 0
6 months
Secondary outcome [8] 262288 0
Change in N-terminal pro-B-type natriuretic peptide (NT pro-BNP) as measured by commercial automated Electrochemiluminescent Immuno Assays (ECLIA) using a Roche E170 Analyser.
Timepoint [8] 262288 0
6 months from randomisation
Secondary outcome [9] 262289 0
Change in Beck Hopelessness Scale (BHS)
Timepoint [9] 262289 0
6 months from randomisation
Secondary outcome [10] 262290 0
Change in perceived social support using the Enhancing Recovery in Coronary Heart Disease (ENRICHD) Social Support Inventory (ESSI)
Timepoint [10] 262290 0
6 months from randomisation
Secondary outcome [11] 262291 0
Change in quality of life as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ)
Timepoint [11] 262291 0
6 months from randomisation

Eligibility
Key inclusion criteria
1. Age = 18 years
2. Systolic heart failure with documented left ventricular ejection fraction (LVEF) < 40% (at some stage of their illness but not necessarily recently) by echocardiography, magnetic resonance imaging, contrast ventriculography, perfusion scanning or gated blood pool scanning (RNVG).
3. If current LVEF > or = 45%, with New York Heart Association (NYHA) Class II – IV functional limitation
4. Optimal, stable CHF therapy. Optimal therapy will include a beta-blocker and an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), unless not tolerated. Stable therapy is defined as having no new chronic heart failure (CHF) drug class introduced in the 8 weeks prior to randomisation
5. Diagnosis of Major or Minor Depression (confirmed by clinical interview)
6. Able to read English, give informed consent and comply with study procedures.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Currently prescribed an anti-depressant, currently being treated by a psychiatrist or receiving any psychological treatment
2. Severe depression (CDS > or = 140 with severity confirmed on interview)
3. Suicidal ideation (> or = 3 on GRID-Hamilton Depression Score (GRID-HAMD) interview or > or = 2 with confirmation by psychiatrist interview )
4. Other severe psychiatric disorder (including psychosis, bipolar disorder, substance abuse, severe personality disorder)
5. Cognitive impairment (Mini-Mental Status Exam< 24)
6. Estimated glomerular filtration rate (eGFR) < 30 ml.min-1
7. Currently enrolled in, or at least 30 days not yet elapsed since ending another trial
8. Any of the following within the previous 3 months that are likely to require a period of psychological adjustment: heart failure admission or insertion of a cardiac device, major illness or surgery, severe psychosocial stressor (bereavement, separation, job loss)
9. Exposure to a traumatic event (e.g. assault, natural disaster, car accident)
10. Female patients of child bearing potential who are pregnant, breast feeding, or not using adequate contraceptive precautions
11. Currently attending or planning to attend cardiac rehabilitation or exercise program during the treatment phase.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation schedule developed and held by the Clinical Trials Section of Coordinating Centre's Pharmacy Department. Allocation communicated to sites by fax/phone.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified (major/minor depression and site); block randomisation generated by Microsoft Excel.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Multi-centre (4 sites)
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary efficacy analyses will involve analyses of variance (using paired t-tests for univariate, normally distributed scores) and of covariance (ANCOVA) to assess the effect of escitalopram from baseline to 6 month on CDS and 17-item HAM-D scores for combined Major and Minor Depression. The ANCOVA will adjust for covariates of age, gender and baseline CDS and HAM-D-17 scores.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
2/04/2010
Actual
5/10/2010
Date of last participant enrolment
Anticipated
Actual
7/02/2017
Date of last data collection
Anticipated
Actual
6/02/2018
Sample size
Target
124
Accrual to date
Final
29
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 14174 0
The Alfred - Prahran
Recruitment postcode(s) [1] 2217 0
3084
Recruitment postcode(s) [2] 2218 0
3095
Recruitment postcode(s) [3] 2219 0
3175
Recruitment postcode(s) [4] 27150 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 244027 0
Charities/Societies/Foundations
Name [1] 244027 0
Heart Foundation
Country [1] 244027 0
Australia
Funding source category [2] 244028 0
Charities/Societies/Foundations
Name [2] 244028 0
Beyond Blue
Country [2] 244028 0
Australia
Primary sponsor type
Hospital
Name
Austin Health
Address
Studley Road
Heidelberg VIC 3084
Country
Australia
Secondary sponsor category [1] 251374 0
Individual
Name [1] 251374 0
Prof David L. Hare
Address [1] 251374 0
Department of Cardiology
HSB 5
Austin Health
Studley Road
Heidelberg VIC 3084
Country [1] 251374 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258132 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 258132 0
Austin Health
Studley Road
Heidelberg VIC 3084
Ethics committee country [1] 258132 0
Australia
Date submitted for ethics approval [1] 258132 0
Approval date [1] 258132 0
19/05/2009
Ethics approval number [1] 258132 0
H2009/03463

Summary
Brief summary
Background: In patients with chronic heart failure (CHF) depression is common, chronic and more severe than in other groups of cardiac patients. Unfortunately, at the present time in this group of patients, depressed mood is rarely screened for, let alone treated. Many patients have a mild form of depression “minor depression” that is debilitating with consequences that are anything but “minor”. We have data that demonstrate that depression (both major and minor) is a marker of a worse future health, including death, in CHF patients. However, these data do not conclusively answer two questions: 1. Does providing antidepressant medication for people with heart failure and depression improve their mood? 2. Does improving mood with antidepressant medication also improve physical functions related to heart health? Aims: This study, therefore, aims to test the hypothesis that treatment with an antidepressant medication (escitalopram) can improve minor and major depression in depressed patients with CHF. The study will also examine whether by reducing depression, other known medical risk factors that are related to both depression and CHF are changed at the same time. A third part of the study will examine whether there are longer term benefits to hospitalizations and longevity, and finally, genetic testing will done to assess the role of certain genes in the response to treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30516 0
Prof David L. Hare
Address 30516 0
Department of Cardiology
HSB Level 5
Austin Hospital
Studley Rd
Heidelberg, VIC 3084
Country 30516 0
Australia
Phone 30516 0
+61 3 9496 3002
Fax 30516 0
Email 30516 0
[email protected]
Contact person for public queries
Name 13763 0
Deidre Toia
Address 13763 0
Department of Cardiology
HSB 5
Austin Health
Studley Road
Heidelberg VIC 3084
Country 13763 0
Australia
Phone 13763 0
Int + 61 3 9496 3652
Fax 13763 0
Int + 61 3 9496 5026
Email 13763 0
[email protected]
Contact person for scientific queries
Name 4691 0
David L. Hare
Address 4691 0
Department of Cardiology
HSB 5
Austin Health
Studley Road
Heidelberg VIC 3084
Country 4691 0
Australia
Phone 4691 0
Int + 61 3 9496 3002
Fax 4691 0
Int + 61 3 9496 5026
Email 4691 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All individual participant data collected during the trial, after deidentification.
When will data be available (start and end dates)?
Immediately following publication. No end date.
Available to whom?
Researchers who provide a methodologically sound proposal.
Available for what types of analyses?
Individual participant data meta-analyses.
How or where can data be obtained?
Proposals should be directed to [email protected]. To gain access, data requestors will need to sign a data access agreement.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
2735Study protocol  [email protected]
2736Statistical analysis plan  [email protected]
2737Informed consent form  [email protected]
2738Clinical study report  [email protected]



Results publications and other study-related documents

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