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Trial registered on ANZCTR


Registration number
ACTRN12612000931875
Ethics application status
Approved
Date submitted
31/08/2012
Date registered
31/08/2012
Date last updated
2/09/2024
Date data sharing statement initially provided
2/09/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Melatonin versus placebo for prevention of delirium in inpatients with advanced cancer
Scientific title
Randomised double blind placebo controlled pilot phase II trial of oral melatonin for the prevention of delirium in hospital in people with advanced cancer
Secondary ID [1] 280115 0
Nil
Universal Trial Number (UTN)
U1111-1133-5010
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced cancer 286033 0
Delirium 286034 0
Condition category
Condition code
Cancer 286222 286222 0 0
Any cancer
Neurological 286223 286223 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral, prolonged-release melatonin (2mg) every night for the duration of inpatient admission.
Intervention code [1] 284447 0
Prevention
Comparator / control treatment
Placebo (amino methacrylate co-polymer tablet)
Control group
Placebo

Outcomes
Primary outcome [1] 286696 0
Percentage of eligible patients screened who progress to be randomised and complete study intervention
Timepoint [1] 286696 0
Discharge or death
Secondary outcome [1] 296481 0
Preliminary data on efficacy of melatonin versus placebo on number of delirium events and time to first incident delirium to inform sample size calculation for a definitive Phase III trial (defined as equal to or greater than 17.75 on Delirium Rating Scale-98-Revised [DRS-98-R])
Timepoint [1] 296481 0
Discharge or death
Secondary outcome [2] 296483 0
Preliminary data on efficacy of melatonin versus placebo on delirium symptom and time profile, subtype, severity and duration (as measured by DRS-98-R)
Timepoint [2] 296483 0
Daily during delirium episodes until discharge or death
Secondary outcome [3] 296484 0
Preliminary data on efficacy of melatonin versus placebo on sleep quality (as measured by Insomnia Severity Index [ISI])
Timepoint [3] 296484 0
Baseline, then every 5 days for duration of inpatient admission
Secondary outcome [4] 296485 0
Preliminary data on toxicity of melatonin, in particular sedation (measured by Richmond Agitation Sedation Scale [RASS])
Timepoint [4] 296485 0
Daily during inpatient admission
Secondary outcome [5] 296486 0
Preliminary data on pathophysiology via levels of neuronal apoptosis markers, and melatonin, serotonin and tryptophan (serum assays)
Timepoint [5] 296486 0
Baseline and upon occurrence of any delirium episodes until discharge or death
Secondary outcome [6] 296487 0
Preliminary data on health outcomes (function, survival, medical complications associated with delirium such as falls, pressure areas, pneumonia) and health services utilisation (length of stay and in hospital resource utilisation) to inform an economic evaluation component of the definitive phase III study
Timepoint [6] 296487 0
Discharge or death

Eligibility
Key inclusion criteria
Diagnosis of advanced cancer defined by the intent of treatment being no longer curative;

Admission to an acute or subacute inpatient palliative care or oncology facility;

Capacity to give written informed consent;

English speaking;

Participant is capable of completing assessments and complying with the study procedures.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Inability to communicate in English;

Inability to take medications orally or via gastrostomy tube;

Delirium on admission as defined by the cut-off score on DRS-98-R equal to or greater than 17.75 indicative of delirium;

Australian Karnofsky Performance Status (AKPS) less than 31;

Known allergy to melatonin or placebo content;

Active seizure disorder defined as seizure within last one month, or seizure disorder not on anticonvulsants (due to pro-convulsive effect of melatonin in children and severe epilepsy);

Concomitant cimetidine use (CYP2D Inhibitor increases melatonin plasma levels by 1.7 fold);

Patients with a current history of abuse of alcohol (alcohol reduces melatonin levels);

In people taking warfarin a markedly nontherapeutic international normalized ratio (INR) defined as less than 1 or more than 4 (due to melatonin both causing increase and decreased INR);

Moderate to severe dementia as defined by clinical diagnosis of dementia and a Short Blessed Test (SBT) score of equal to or greater than 10;

Current use of melatonin for other indication, or use of melatonin within last 14 days;

Pregnancy or breastfeeding;

Participants who have participated in a clinical study of a new chemical entity within the month prior to study entry.

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)
At each centre, people referred to the study will be sequentially allocated an ID number. This ID number will be used for all subsequent study documentation for that participant.

On notification of a participant, the pharmacist at each site will consult the strata table according to the strata determined by supplied randomization schedule, and will allocate the next code available according to the supplied strata table and dispensed the active or inactive medicine delivered in the labeled bottle. The participant ID, allocation code, dates of request, preparation, and dispensing will be recorded in a log maintained by the pharmacist and supplied to the central registry on each randomisation.

At all times, from eligibility screening to completion of the study, all study staff are unaware of the treatment allocation. Allocation is concealed from the investigator at the time of the participant inclusion in the trial; the allocation is determined by contacting the site pharmacy.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation schedules will be developed for each site using random number tables, generated at an independent central registry. Treatment for each participant will be allocated according to a block randomisation schedule in a 1:1 ratio. Block randomisation will ensure even allocation to each code. The central registry will supply site randomisation schedules to each site pharmacy. There will be stratification at the randomisation level for this study by site of admission (palliative care and oncology).
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
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
3/06/2014
Actual
9/07/2014
Date of last participant enrolment
Anticipated
Actual
12/03/2015
Date of last data collection
Anticipated
Actual
30/03/2015
Sample size
Target
30
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 2583 0
Braeside Hospital - Prairiewood
Recruitment hospital [2] 2584 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [3] 2585 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [4] 2586 0
Barwon Health - McKellar Centre campus - North Geelong
Recruitment hospital [5] 27064 0
Sacred Heart Hospice - Darlinghurst
Recruitment postcode(s) [1] 5589 0
2164
Recruitment postcode(s) [2] 5590 0
2310
Recruitment postcode(s) [3] 8258 0
3050 - Royal Melbourne Hospital
Recruitment postcode(s) [4] 8259 0
3215 - North Geelong
Recruitment postcode(s) [5] 43131 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 285909 0
Government body
Name [1] 285909 0
Cancer Institute NSW
Country [1] 285909 0
Australia
Primary sponsor type
University
Name
Flinders University
Address
Flinders Drive, Bedford Park, SA 5042.
Country
Australia
Secondary sponsor category [1] 283757 0
None
Name [1] 283757 0
Address [1] 283757 0
Country [1] 283757 0
Other collaborator category [1] 260617 0
Hospital
Name [1] 260617 0
Bruyere Continuing Care
Address [1] 260617 0
Palliative Care Administration
Bruyere Continuing Care
43 Rue Bruyere St
Ottawa
Ontario
K1N 5C8
Country [1] 260617 0
Canada

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287836 0
Cancer Institute NSW
Ethics committee address [1] 287836 0
Ethics committee country [1] 287836 0
Australia
Date submitted for ethics approval [1] 287836 0
Approval date [1] 287836 0
10/07/2012
Ethics approval number [1] 287836 0
HREC/12/CIC/8
Ethics committee name [2] 291132 0
South Western Sydney Local Health District
Ethics committee address [2] 291132 0
Ethics committee country [2] 291132 0
Australia
Date submitted for ethics approval [2] 291132 0
20/11/2013
Approval date [2] 291132 0
10/12/2013
Ethics approval number [2] 291132 0
HREC/13/LPOOL/350

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33900 0
A/Prof Meera Agar
Address 33900 0
Braeside Hospital, Locked Bag 82, Wetherill Park, NSW 2164
Country 33900 0
Australia
Phone 33900 0
+61 2 9616 8654
Fax 33900 0
+61 2 9616 8657
Email 33900 0
meera.agar@sswahs.nsw.gov.au
Contact person for public queries
Name 17147 0
Tim Luckett
Address 17147 0
University of Technology Sydney (UTS), Faculty of Health, Building 10, Level 7, 235-253 Jones St, Ultimo, NSW 2007
Country 17147 0
Australia
Phone 17147 0
+61 2 9514 4861
Fax 17147 0
+61 2 9514 4474
Email 17147 0
t.luckett@unsw.edu.au
Contact person for scientific queries
Name 8075 0
Meera Agar
Address 8075 0
Braeside Hospital, Locked Bag 82, Wetherill Park, NSW 2164
Country 8075 0
Australia
Phone 8075 0
+61 2 9616 8654
Fax 8075 0
+61 2 9616 8657
Email 8075 0
meera.agar@sswahs.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.