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Trial registered on ANZCTR


Registration number
ACTRN12619000034134
Ethics application status
Approved
Date submitted
8/01/2019
Date registered
11/01/2019
Date last updated
21/04/2022
Date data sharing statement initially provided
11/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Melatonin for Delirium Reduction, Resolution And Mitigation of Abnormal Arousal (MelaDRRAMAA)
Scientific title
Melatonin for Delirium Reduction, Resolution And Mitigation of Abnormal Arousal (MelaDRRAMAA): a double blinded placebo-controlled randomised trial of Melatonin 5mg nightly for 5 nights for the reduction of severity of delirium in older adult medical inpatients
Secondary ID [1] 296082 0
nil
Universal Trial Number (UTN)
U1111-1226-3728
Trial acronym
MelaDRRAMAA
Linked study record
Definitive trial following pilot trial: ACTRN12614000101684

Health condition
Health condition(s) or problem(s) studied:
Delirium 310970 0
Condition category
Condition code
Neurological 309633 309633 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Melatonin 5mg oral capsule nightly for 5 days administered directly by hospital nursing staff.
Intervention code [1] 313274 0
Treatment: Drugs
Comparator / control treatment
Placebo - identical capsule but for active ingredient.
Control group
Placebo

Outcomes
Primary outcome [1] 318590 0
Symptoms of Delirium - Memorial Delirium Assessment Scale (MDAS) - during treatment phase
Timepoint [1] 318590 0
Change from baseline to mean MDAS over days 1-5
Secondary outcome [1] 365451 0
Symptoms of Delirium - Memorial Delirium Assessment Scale (MDAS) - Post treatment phase
Timepoint [1] 365451 0
Following treatment cessation on days 6 and 7 of the trial (medication on days 1-5)
Secondary outcome [2] 365452 0
Normal level of arousal - proportion of time with a Richmond Agitation and Sedation Scale of zero.
Timepoint [2] 365452 0
Days 1-5 - daily - during treatment phase
Secondary outcome [3] 365453 0
Duration of delirium - number of days Confusion Assessment Method (CAM) positive
Timepoint [3] 365453 0
Days 1-5 - daily - during treatment phase
Secondary outcome [4] 365454 0
Number of uses of medications for delirium- Number of uses of rescue medications (Benzodiazepines, Antipsychotics) - assessed by chart review
Timepoint [4] 365454 0
Days 1-5 - daily - during treatment phase
Secondary outcome [5] 365460 0
Number of uses of physical restraint as assessed by inspection and chart review
Timepoint [5] 365460 0
Days 1-5 - daily - during treatment phase
Secondary outcome [6] 365464 0
Proportion of participants with a new clinical diagnosis of dementia by clinical assessment by geriatrician at 6 month follow-up visit
Timepoint [6] 365464 0
6 month follow-up
Secondary outcome [7] 365466 0
Sleep quality - MDAS item 10 score
Timepoint [7] 365466 0
Days 1-5 - daily - during treatment phase
Secondary outcome [8] 408978 0
Cognition at 6 month follow up (standardised MMSE)
Timepoint [8] 408978 0
6 months follow-up
Secondary outcome [9] 408979 0
Neurofilament light levels in serum at baseline, 5-7 days and at 6 month follow-up.
Timepoint [9] 408979 0
Baseline vs. 6 months
Secondary outcome [10] 408980 0
Cost effectiveness (Cost to healthcare system (Australian dollars)) evaluated by linkage to hospital clinical coding data, medicare utilisation data and Pharmaceutical Benefit Scheme Records.
Timepoint [10] 408980 0
6 months follow-up

Eligibility
Key inclusion criteria
Diagnosis of delirium (regardless of cause)
Inpatient of the Royal Melbourne Hospital
Minimum age
65 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- exclusively hypoactive delirium,
- recent stroke (<14 days),
- sensory impairment or dysphasia or language such that not evaluable,
- planned for surgery,
- prognosis <7days,
- severe hepatic failure
- allergy or intolerance to melatonin or excipients.
- Treated with Melatonin or melatonin agonists within 24 hours prior to enrolment

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)
Permuted block opaque envelopes with random allocation by trial pharmacist
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block stratified according to diagnosis with cognitive impairment
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
The primary and secondary outcome measures will be compared using a Students’ t-test for normally distributed data or Mann-Whitney for non-normally distributed continuous variables. For discrete outcomes, results will be tested using a Chi-square test. Missing data will be handled for the analysis using the last observation carried forward method as per protocol. A p value of less than 0.05 will be considered significant, two sided where appropriate.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/06/2019
Actual
11/03/2021
Date of last participant enrolment
Anticipated
1/12/2019
Actual
7/03/2022
Date of last data collection
Anticipated
14/09/2022
Actual
Sample size
Target
120
Accrual to date
Final
120
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 12838 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 25308 0
3050 - Royal Melbourne Hospital
Recruitment postcode(s) [2] 25309 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 300673 0
Hospital
Name [1] 300673 0
Royal Melbourne Hospital
Country [1] 300673 0
Australia
Primary sponsor type
Hospital
Name
Royal Melbourne Hospital
Address
Grattan street,
Parkville, VIC 3050
Country
Australia
Secondary sponsor category [1] 301269 0
None
Name [1] 301269 0
None
Address [1] 301269 0
n/a
Country [1] 301269 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301455 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 301455 0
Grattan street,
Parkville, VIC 3050
Ethics committee country [1] 301455 0
Australia
Date submitted for ethics approval [1] 301455 0
07/03/2019
Approval date [1] 301455 0
15/07/2020
Ethics approval number [1] 301455 0

Summary
Brief summary
Delirium is the sudden onset of confusion or hallucinations, due to an illness or medication. It affects the elderly particularly, and is both distressing to the sufferer and their carers, as well as causing death, disability and institutionalisation.
Melatonin is a naturally occurring hormone in the human brain important in sleep. Sleep is disturbed in delirium, and studies have shown melatonin can prevent delirium.
This study aims to determine whether Melatonin 5mg in oral capsules given nightly for 5 nights can treat and cure delirium that has developed in older patients in hospital.
Trial website
None.
Trial related presentations / publications
None.
Public notes
Delirium is the sudden onset of confusion or hallucinations, due to an illness or medication. It affects the elderly particularly, and is both distressing to the sufferer and their carers, as well as causing death, disability and institutionalisation.

Melatonin is a naturally occurring hormone in the human brain important in sleep. Sleep is disturbed in delirium, and studies have shown melatonin can prevent delirium. Low dose melatonin prevented most delirium, but did not reduce the severity of delirium when it occurred. Moderate dose melatonin also prevented most delirium, and was reported to reduce the severity of delirium when it occurred, but this was not demonstrated using a validated scoring scale, or evaluated statistically, ie not properly demonstrated.

There is no easily used marker of delirium other than observation – cure from delirium is observed when symptoms resolve. A treatment that causes symptomatic improvement that continues once the treatment has stopped can be said to cure, or at least abate delirium. No treatment has been shown to cure or abate delirium once developed.

The group conducted a pilot trial that demonstrated that Melatonin 5mg was safe in this group of patients, and that 120 patients would be required to show that Melatonin 5mg had a clinically and statistically significant effect on delirium severity.

This subsequent study aims to determine whether moderate dose Melatonin is effective in treating the symptoms of delirium, and shortening the overall duration of delirium after treatment ceases (abates or cures delirium).

To study this, elderly patients admitted to the Royal Melbourne Hospital with delirium, and not requiring surgery, will be recruited with suitable consent to receive either 5mg melatonin oral capsule (60 patients) or inactive placebo (60 patients) nightly for 5 nights (or until discharged). All patients will receive all standard treatment for delirium as well. During treatment and for two further days, participants will be assessed using a validated scale of delirium severity (the Memorial Delirium Assessment Scale), and a validated measure of delirium state (Confusion Assessment Method) to determine if Melatonin decreases the severity and/or the duration of delirium, and abates delirium.

Arousal (the level of alertness) can also be altered in delirium, this will be measured, as will sleep, and the number of uses of restraints, medications, falls and pressure areas (bed sores), with the hypothesis that melatonin will reduce the use of restraints and medications for delirium and not increase falls and pressure areas.

Should Melatonin be successful in treating the symptoms of delirium, it would be one of only a few treatments that do so, and likely to be a safe and relatively side-effect free compared to other established treatments, substantially improving treatment of delirium. Should Melatonin abate delirium that has developed, it would be the only treatment shown to do so.

Contacts
Principal investigator
Name 87062 0
A/Prof Peter W Lange
Address 87062 0
The Royal Melbourne Hospital
Grattan Street,
Parkville, VIC 3050
Country 87062 0
Australia
Phone 87062 0
+61 0393427000
Fax 87062 0
Email 87062 0
[email protected]
Contact person for public queries
Name 87063 0
Peter W Lange
Address 87063 0
The Royal Melbourne Hospital
Grattan Street,
Parkville, VIC 3050
Country 87063 0
Australia
Phone 87063 0
+61 0393427000
Fax 87063 0
Email 87063 0
[email protected]
Contact person for scientific queries
Name 87064 0
Peter W Lange
Address 87064 0
The Royal Melbourne Hospital
Grattan Street,
Parkville, VIC 3050
Country 87064 0
Australia
Phone 87064 0
+61 0393427000
Fax 87064 0
Email 87064 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 of the individual participant data collected during the trial, after de-identification
When will data be available (start and end dates)?
After trial completion and analysis. - 10/08/2020. Records will be held for 7 years and therefore available until 10/08/2027.
Available to whom?
Researchers who provide a methodologically sound proposal and comply with relevant Australian laws, pursuant to HREC approval.
Available for what types of analyses?
Analyses proposed by researchers who provide a methodologically sound proposal and comply with relevant Australian laws, pursuant to HREC approval.
How or where can data be obtained?
Access subject to individual approval by Principal Investigator, compliant with relevant Australian laws, pursuant to HREC approval.


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.