Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000819527
Ethics application status
Approved
Date submitted
21/07/2015
Date registered
10/08/2015
Date last updated
20/01/2020
Date data sharing statement initially provided
20/01/2020
Date results information initially provided
20/01/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
The Healthy Heart-Mind Trial: Efficacy of melatonin for decreasing the incidence and severity of delirium following cardiac surgery
Scientific title
The Healthy Heart-Mind Trial: Efficacy of melatonin versus placebo for decreasing the incidence and severity of delirium following cardiac surgery in adults
Secondary ID [1] 287129 0
Nil
Universal Trial Number (UTN)
U1111-1172-4046
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
delirium 295666 0
cardiac surgery 295667 0
Condition category
Condition code
Mental Health 295944 295944 0 0
Other mental health disorders
Surgery 296019 296019 0 0
Other surgery
Cardiovascular 296020 296020 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
melatonin 3mg oral capsules once daily for 7 days (2 days prior and 5 days after surgery). Medication adherence monitored through pill count and review of medication charts
Intervention code [1] 292380 0
Prevention
Intervention code [2] 292447 0
Treatment: Drugs
Comparator / control treatment
microcrystalline cellulose placebo capsules
Control group
Placebo

Outcomes
Primary outcome [1] 295623 0
The primary outcome of interest for this trial is the difference in the incidence of delirium (as determined by the Confusion Assessment Method and DSM-5 criteria) between the groups after cardiac surgery.
Timepoint [1] 295623 0
7 days
Secondary outcome [1] 316023 0
Severity of delirium as assessed with the Memorial Delirium Assessment Scale
Timepoint [1] 316023 0
Assessed daily for 7 days or until discharge
Secondary outcome [2] 316024 0
Duration of delirium
Timepoint [2] 316024 0
Assessed daily with Confusion Assessment Method and DSM 5 criteria from day 1 post surgery until discharge
Secondary outcome [3] 316025 0
Use of psychiatric medications during admission - assessed by review of medication charts
Timepoint [3] 316025 0
From admission to hospital discharge
Secondary outcome [4] 316026 0
Change in cognitive performance at discharge and 3 months as measured by Telephone Interview for Cognitive Status
Timepoint [4] 316026 0
Cognition assessed at baseline (enrollment), day 7 post surgery or day of discharge and at 3 months post surgery
Secondary outcome [5] 316027 0
Mood and anxiety symptoms as rated by Hospital Anxiety and Depression Scale
Timepoint [5] 316027 0
Assessed at baseline, day7/hospital discharge and 3 months after surgery
Secondary outcome [6] 316232 0
Hospital length of stay
Timepoint [6] 316232 0
Assessed at time of discharge

Eligibility
Key inclusion criteria
1. Aged 50 years and older
2. Undergoing elective or semi-elective cardiac surgery (on or off cardiopulmonary bypass) for coronary artery bypass grafting (CABG) and/or valvular surgery
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Decline or are unable to give informed consent
2. Are undergoing emergency surgery
3. Are not fluent in written or spoken English (for the purposes of being able to complete the study assessments and questionnaires)
4. Have a contraindication to taking melatonin, such as a prior allergic reaction
5. Are currently using melatonin
6. Have a diagnosis of dementia or score 19 or less on the Telephone Interview for Cognitive Status
7. Score 15 or greater on the alcohol use disorders identification test (AUDIT)

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
We will recruit 210 participants undergoing elective/semi-elective cardiac surgery in Perth, Western Australia. Participants will be randomly allocated to melatonin 3mg or matching placebo. The randomisation list will be generated and maintained by the hospital pharmacy and not accessible to the investigators.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised to treatment with melatonin or matching placebo on a ratio of 1:1 according to a list of computer-generated random numbers.
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
Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
Baseline data will be compared using descriptive statistics, Student t tests for normally distributed continuous variables, Mann-Whitney test for skewed variables and Pearson’s chi-square statistic for categorical variables. Analyses will be based on completers and intention-to-treat. The primary hypothesis (difference in the proportion of participants who develop delirium) will be tested using intention-to-treat analysis of panel data (xtlogit). This approach to the analysis of the data allows for the inclusion of all available information and for the investigation of interactions between terms (such as intervention and time). A similar approach will be used to analyse other binary outcomes (e.g., use of psychotropic medication). We will use multilevel mixed models to investigate changes in scores of the MDAS and TICS (continuous variables). All probability tests will be two-tailed and will be declared as significant when p<0.05.

We based our sample size on a previous trial (Al-Aama et al. 2011) that reported a 15.6% absolute reduction (19.2% versus 3.6%, p<0.02) in the incidence of delirium in their sample. Assuming a 15.6% absolute risk reduction in our patients with a conservative 25% incidence of delirium in the control group and an incidence of 9.4% in the intervention group, we will require 91 participants per group (182 participants in total) to detect a difference of this magnitude with a power of 80% and a two-sided alpha of 0.05. Allowing for a drop out rate of around 15%, we plan to recruit 210 participants.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/10/2015
Actual
2/02/2016
Date of last participant enrolment
Anticipated
31/05/2018
Actual
10/07/2018
Date of last data collection
Anticipated
Actual
2/10/2018
Sample size
Target
210
Accrual to date
Final
210
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 4065 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [2] 12055 0
St John of God Hospital, Subiaco - Subiaco
Recruitment postcode(s) [1] 10013 0
6009 - Broadway Nedlands
Recruitment postcode(s) [2] 24212 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 291683 0
Government body
Name [1] 291683 0
WA Department of Health
Country [1] 291683 0
Australia
Primary sponsor type
University
Name
University of Western Australia
Address
35 Stirling Highway
Crawley
WA
6009
Country
Australia
Secondary sponsor category [1] 290360 0
None
Name [1] 290360 0
Address [1] 290360 0
Country [1] 290360 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293212 0
Sir Charles Gairdner Hospital
Ethics committee address [1] 293212 0
Hospital Avenue
Nedlands
Perth
WA 6009
Ethics committee country [1] 293212 0
Australia
Date submitted for ethics approval [1] 293212 0
22/07/2015
Approval date [1] 293212 0
17/09/2015
Ethics approval number [1] 293212 0
2015-118

Summary
Brief summary
Delirium is common in patients recovering from surgical procedures, particularly those involving major cardiac surgery. It is associated with numerous adverse consequences, including increased patient suffering, longer hospital stays, increased postoperative complications, increased mortality and poorer cognitive outcomes. Current strategies are only modestly effective in treating delirium and the cornerstone of management is prevention, however even best practice multifactorial interventions only result in a modest reduction in delirium incidence. Melatonin is a naturally occurring compound that is important in the regulation of sleep. Melatonin metabolism dysregulation has been implicated in the development of delirium, although only sparse evidence about its possible role in delirium prevention exists.

The main aim of this randomised, placebo-controlled, double blind clinical trial is to determine if 3mg melatonin can reduce the incidence, severity and complications of delirium following cardiac surgery.

We plan to enrol 210 participants due to undergo elective cardiac surgery. Participants will be randomly allocated to melatonin 3mg or matching placebo for 7 days beginning two nights prior to the scheduled surgery. We are primarily interested in whether those given melatonin have a lower rate of new-onset delirium but will also be interested to see if they experience less delirious symptoms, less depression and anxiety, less cognitive impairment, require less medications during their admission (especially sedative medications) and have shorter stays in hospital and ICU.

Melatonin is safe, inexpensive and readily available and thus offers a potentially simple, cost effective intervention suitable for use in routine clinical practice.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 58934 0
Dr Andrew Ford
Address 58934 0
University of Western Australia (M573)
35 Stirling Highway
Crawley
Western Australia
6009
Country 58934 0
Australia
Phone 58934 0
+61892242855
Fax 58934 0
Email 58934 0
[email protected]
Contact person for public queries
Name 58935 0
Dr Andrew Ford
Address 58935 0
University of Western Australia (M573)
35 Stirling Highway
Crawley
Western Australia
6009
Country 58935 0
Australia
Phone 58935 0
+61892242855
Fax 58935 0
Email 58935 0
[email protected]
Contact person for scientific queries
Name 58936 0
Dr Andrew Ford
Address 58936 0
University of Western Australia (M573)
35 Stirling Highway
Crawley
Western Australia
6009
Country 58936 0
Australia
Phone 58936 0
+61892242855
Fax 58936 0
Email 58936 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Ford et al. The Healthy Heart-Mind Trial: Randomiz... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseThe Healthy Heart-Mind trial: Melatonin for prevention of delirium following cardiac surgery: Study protocol for a randomized controlled trial.2016https://dx.doi.org/10.1186/s13063-016-1163-1
EmbaseThe Healthy Heart-Mind Trial: Randomized Controlled Trial of Melatonin for Prevention of Delirium.2020https://dx.doi.org/10.1111/jgs.16162
N.B. These documents automatically identified may not have been verified by the study sponsor.