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Trial registered on ANZCTR


Registration number
ACTRN12620000661976
Ethics application status
Approved
Date submitted
21/04/2020
Date registered
9/06/2020
Date last updated
9/06/2020
Date data sharing statement initially provided
9/06/2020
Date results information initially provided
9/06/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Improving sleep in Intensive Care
Scientific title
Effect of Exogenous Melatonin Administration in Critically Ill Patients on Delirium and Sleep: A Randomized Controlled Trial.
Secondary ID [1] 301026 0
"Nil Known"
Universal Trial Number (UTN)
U1111-1250-6226
Trial acronym
MELATICU
Linked study record
Not Applicable

Health condition
Health condition(s) or problem(s) studied:
Sleep deprivation 317141 0
ICU delirium 317142 0
Critical illness 317408 0
Condition category
Condition code
Anaesthesiology 315294 315294 0 0
Other anaesthesiology

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Drug name: Melatonin (Generic name)
Dose administered: 6 mg during 7 time points between 9pm and 01 am, as follows:

Real drug administration time schedule Time (hours. minutes in relation to melatonin dose) Measurement / sample
21h 0.00 First 3mg dose of study drug
0.00 Blood sample 1
0.30 Blood sample 2
0.45 Blood sample 3
1.00 Blood sample 4
22h 1.00 Administration of 0.5mg study drug
1.30 Blood sample 5
2.00 Blood sample 6
23h 2.00 Administration of 0.5mg study drug
24h 3.00 Administration of 0.5mg study drug
01h 4.00 Administration of 0.5mg study drug
02h 5.00 Administration of 0.5mg study drug
03 h 6.00 Administration of 0.5mg study drug
7.00 Blood sample 7
9.00 Blood sample 8


Duration of administration: Five consecutive nights
Mode of administration: syrup (Enteral administration)

Such intervention will be monitored through the clinical audit tool (Metavision) and CIS (Clinical Information System) at the bedside

Assessment completion on the last day of recruitment, day five of intervention
Intervention code [1] 317379 0
Prevention
Intervention code [2] 317380 0
Treatment: Drugs
Comparator / control treatment
Placebo was a sucrose solution
Control group
Placebo

Outcomes
Primary outcome [1] 323536 0
Primary outcome measure:
1) number of Sleep arousal
By utilising the gold standard for sleep recording: polysomnogram
Timepoint [1] 323536 0
Primary outcome measure on the last day of the intervention (day 5 of intervention)
This will be a second and last polysomnogram recording which will be done on the last day of drug / placebo
Primary outcome [2] 323750 0
2) length of sleep REM phase
Utilising the gold standard measure for sleep assessment: polysomnogram
Timepoint [2] 323750 0
Same timepoint than for first outcome measure, day 5 of recruitment
Secondary outcome [1] 382186 0
Change in ICU related delirium assessed by applying the CAM and RASS scales which are the validated scales for Delirium and Agitation in Critical care


Timepoint [1] 382186 0
Measured at the end of the intervention (day 5 after initiating melatonin / placebo)

Eligibility
Key inclusion criteria
* Ventilated patients in their weaning phase
* Integrity of the enteral system (capacity to absorb enteral medication)

All patients will be ICU inpatients
Minimum age
18 Years
Maximum age
90 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-- Patients with an inflammatory response
-- Septic patients
-- Burns
-- Patients on vasopressors
-- Patients with underlying psychiatric disorders on baseline antipsychotic medications

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 to either group was concealed.
Use of random number generators and enclosed envelopes to allocate patients into groups
Allocation was performed by a third party: research coordinators without the investigators ' involvement
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerized sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?

The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
N/A
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
For this Phase II study, a significant reduction in relative risk was planned to determine a significant clinical signal. Using a reduction in delirium from 30% to 5% with a significance level of 5% and a power of 80%, 86 patients in total were meant to enroll. Data was analyzed on an intention to treat basis. The study was designed with the guidelines of the CONSORT statement to adhere to requirements for randomized controlled trials. Univariate data was described using medians with interquartile ranges (IQR) and 95% confidence intervals (95%CI) unless otherwise specified. Univariate analysis used chi-square, Fisher’s exact, Wilcoxon rank sum and Kruskal-Wallis tests as appropriate. Analysis used Stata 15.1 statistical software (College Station, Texas. United States of America).

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 16509 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 30066 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 305471 0
Charities/Societies/Foundations
Name [1] 305471 0
RBWH Research Foundation - Queensland Health 2011
Address [1] 305471 0
Royal Brisbane and Womens' Hospital-Research Foundation
Butterfield Street
Herston 4029
QLD
Country [1] 305471 0
Australia
Primary sponsor type
University
Name
University of Queensland
Address
St Lucia QLD 4072
Country
Australia
Secondary sponsor category [1] 305923 0
None
Name [1] 305923 0
Address [1] 305923 0
Country [1] 305923 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305787 0
Metro North Hospitals and Health Service HREC
Ethics committee address [1] 305787 0
Level 13, Block 7, Royal Brisbane and Women’s Hospital, Butterfield street, HERSTON QLD 4029
Ethics committee country [1] 305787 0
Australia
Date submitted for ethics approval [1] 305787 0
21/09/2009
Approval date [1] 305787 0
16/12/2009
Ethics approval number [1] 305787 0
HREC/09/QRBW/262

Summary
Brief summary
This is a study attempting to treat delirium in critically ill patients, by improving the quality and length of their sleep.

The main hypothesis is that the bright and noisy environment within Intensive Care units difficult patients' sleep and those who sleep, have fragmented and shallow (non-restorative) sleep.

The intervention is based on the administration of melatonin, a safe drug that has been shown to improve sleep in other groups of people.

Trial website
N/A
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101594 0
Dr Judith Bellapart
Address 101594 0
Royal Brisbane and Women's Hospital
Department of Intensive Care
3rd Level Ned Hanlon Building
Butterfield Street
Herston 4029
QLD
Country 101594 0
Australia
Phone 101594 0
+61 736468897
Fax 101594 0
+61754338706
Email 101594 0
judith.bellapart@health.qld.gov.au
Contact person for public queries
Name 101595 0
Dr judith Bellapart
Address 101595 0
Royal Brisbane and Women's Hospital
Department of Intensive Care
3rd Level Ned Hanlon Building
Butterfield Street
Herston 4029
QLD
Country 101595 0
Australia
Phone 101595 0
+61 447177585
Fax 101595 0
Email 101595 0
judithbellapart@gmail.com
Contact person for scientific queries
Name 101596 0
Dr Judith Bellapart
Address 101596 0
Royal Brisbane and Women's Hospital
Department of Intensive Care
3rd Level Ned Hanlon Building
Butterfield Street
Herston 4029
QLD
Country 101596 0
Australia
Phone 101596 0
+61 736468897
Fax 101596 0
+61754338706
Email 101596 0
judith.bellapart@health.qld.gov.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 publication: Beginning 30th July 2020 and end date 30th December 2020
Available to whom?
Only researchers who provide a methodologically sound proposal.
Available for what types of analyses?
To achieve the aims in the approved proposal
How or where can data be obtained?
Access subject to approvals by Principal Investigator : judith.bellapart@health.qld.gov.au

What supporting documents are/will be available?
Study protocol
Ethical approval
How or where can supporting documents be obtained?
Type [1] 7690 0
Study protocol
Citation [1] 7690 0
Link [1] 7690 0
Email [1] 7690 0
judith.bellapart@health.qld.gov.au
Other [1] 7690 0
Type [2] 7691 0
Ethical approval
Citation [2] 7691 0
Link [2] 7691 0
Email [2] 7691 0
judithbellapart@gmail.com
Other [2] 7691 0
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – plain English summary
Research question:
Does a "good quality" sleep, reduce the incidence of ICU related delirium?

Background:
Despite all the studies conducted to date, exogenous administration of melatonin in critically ill patients has shown to significantly increase plasma levels of melatonin. This study aims to demonstrate a correlation between plasma levels of melatonin, an improvement on the sleep architecture or a reduction in ICU related delirium.

Participant characteristics:
A sample of critically ill patients in the recovery phase of their disease were consecutively recruited to a double-blind placebo-controlled trial of 6 mg enteral melatonin versus placebo via a nasogastric feeding tube. Inclusion criteria included: patients expected to have a minimal length of 5 days of respiratory weaning, vasopressor free and with preserved absorption (defined as aspirates lesser than 400 ml 4th hourly), absence of ileus and discontinuation of sedation.

Key results:
Baseline delirium and agitation scores showed no statistical difference between groups when compared to post-intervention scores.
Sleep studies were comparable between both groups. The arousal index (number of arousals per hour of sleep) post-intervention was not statistically different when compared to placebo or baseline.

Limitations:
Slow recruitment leading to an earlier termination