ANZCTR - Registration

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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]

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

Condition category

Condition code

Neurological

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]

Treatment: Drugs

Comparator / control treatment

Placebo - identical capsule but for active ingredient.

Control group

Placebo

Outcomes

Primary outcome [1]

Symptoms of Delirium - Memorial Delirium Assessment Scale (MDAS) - during treatment phase

Timepoint [1]

Change from baseline to mean MDAS over days 1-5

Secondary outcome [1]

Symptoms of Delirium - Memorial Delirium Assessment Scale (MDAS) - Post treatment phase

Timepoint [1]

Following treatment cessation on days 6 and 7 of the trial (medication on days 1-5)

Secondary outcome [2]

Normal level of arousal - proportion of time with a Richmond Agitation and Sedation Scale of zero.

Timepoint [2]

Days 1-5 - daily - during treatment phase

Secondary outcome [3]

Duration of delirium - number of days Confusion Assessment Method (CAM) positive

Timepoint [3]

Days 1-5 - daily - during treatment phase

Secondary outcome [4]

Number of uses of medications for delirium- Number of uses of rescue medications (Benzodiazepines, Antipsychotics) - assessed by chart review

Timepoint [4]

Days 1-5 - daily - during treatment phase

Secondary outcome [5]

Number of uses of physical restraint as assessed by inspection and chart review

Timepoint [5]

Days 1-5 - daily - during treatment phase

Secondary outcome [6]

Proportion of participants with a new clinical diagnosis of dementia by clinical assessment by geriatrician at 6 month follow-up visit

Timepoint [6]

6 month follow-up

Secondary outcome [7]

Sleep quality - MDAS item 10 score

Timepoint [7]

Days 1-5 - daily - during treatment phase

Secondary outcome [8]

Cognition at 6 month follow up (standardised MMSE)

Timepoint [8]

6 months follow-up

Secondary outcome [9]

Neurofilament light levels in serum at baseline, 5-7 days and at 6 month follow-up.

Timepoint [9]

Baseline vs. 6 months

Secondary outcome [10]

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]

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?

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]

Royal Melbourne Hospital - City campus - Parkville

Recruitment postcode(s) [1]

3050 - Royal Melbourne Hospital

Recruitment postcode(s) [2]

3050 - Parkville

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Royal Melbourne Hospital

Address [1]

Grattan street,
Parkville, VIC 3050.

Country [1]

Australia

Primary sponsor type

Hospital

Name

Royal Melbourne Hospital

Address

Grattan street,
Parkville, VIC 3050

Country

Australia

Secondary sponsor category [1]

None

Name [1]

None

Address [1]

n/a

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Melbourne Health Human Research Ethics Committee

Ethics committee address [1]

Grattan street,
Parkville, VIC 3050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

07/03/2019

Approval date [1]

15/07/2020

Ethics approval number [1]

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

A/Prof Peter W Lange

Address

The Royal Melbourne Hospital
Grattan Street,
Parkville, VIC 3050

Country

Australia

Phone

+61 0393427000

Fax

peter.lange@mh.org.au

Contact person for public queries

Name

Peter W Lange

Address

The Royal Melbourne Hospital
Grattan Street,
Parkville, VIC 3050

Country

Australia

Phone

+61 0393427000

Fax

peter.lange@mh.org.au

Contact person for scientific queries

Name

Peter W Lange

Address

The Royal Melbourne Hospital
Grattan Street,
Parkville, VIC 3050

Country

Australia

Phone

+61 0393427000

Fax

peter.lange@mh.org.au

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.

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