A randomised trial of the pro-phylactic use of melatonin in critically ill patients to evaluate if this leads to a reduction in incidence of delirium (Pro-MEDIC study)

Curtin University

Dataset description

Rationale Delirium is defined as acute organic brain dysfunction characterised by inattention and disturbance of cognition. It is common in the intensive care unit and is associated with poorer outcomes. Good quality sleep is important in the prevention and management of delirium. Melatonin is a natural hormone secreted by the pineal gland which helps in the regulation of the sleep-wake cycle. It is possible that melatonin supplementation in intensive care improves sleep and prevents delirium. Methods and design The 'Prophylactic Melatonin for Delirium in Intensive Care' study is a multi-centre, randomised, double-blinded, placebo-controlled trial. The primary objective of this study is to determine whether melatonin given prophylactically decreases delirium in critically ill patients. A total of 850 ICU patients have been randomised (1:1) to receive either melatonin or a placebo. Participants were monitored twice daily for symptoms of delirium. Results This paper and the attached additional files describe the statistical analysis plan (SAP) for the trial. The SAP has been developed and submitted for publication before the database has been locked and before the treatment allocation has been unblinded. The SAP contains details of analyses to be undertaken, which will be reported in the primary and secondary publications.
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Source Study




Phase 2 / Phase 3


Government body,State Health Research Advisory Council

Scientific enquiries

Dr Bradley Wibrow

Brief Summary

Aim Delirium is associated with increased mortality, ventilator time, hospital length of stay, poor functional status and cognitive impairment, use of physical restraints and medical costs. This study will help determine whether the use of melatonin prophylactically decreases the incidence of delirium in Intensive Care patients. Secondary aims will be to see if melatonin prophylaxis via its effect on delirium and sleep results in reduced mortality, length of stay (hospital and ICU), ventilator d ....
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Key Inclusion Criteria

Patients admitted to the Intensive Care Unit, identified by the treating intensivist as expected to have an ICU length of stay >72 hours. Patients must be enrolled within 48 hours of their ICU admission.

Key Exclusion Criteria

1 Patients already on melatonin before their admission to ICU 2 Prior hypersensitivity reaction to any of the components of the study drug 3 Patients expected to be discharged within 72 hrs of their ICU admission 4 Non English speaking 5 Expected or inevitable death within next 48 hours 6 Patients that are not expected to improve adequately to be able to be assessed with a CAM-ICU score during their ICU stay 7 Patients that are not able to be assessed due to neurological problems that would affe ....
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Can healthy volunteers participate?




Sample Size    850

Min. age    18 Years

Max. age    No limit

Sex    Both males and females

Condition category    Delirium

Condition code    Neurological


Intervention code Prevention , Treatment: Drugs

Melatonin (4mg) to be given once daily at 21:00 (oral or nasogastric medication) to intensive care patients who have an expected ICU length of stay >72 hrs. Patients must be enrolled within 48 hrs of their admission. Given for 14 days or until ICU discharge (whichever is shorter). The decision on whether nasogastric or oral route is used will be left up to the patient and bedside nurse. Melatonin is inexpensive with an excellent safety profile and is widely used in the community. It is a natural ....
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Control group Placebo

Placebo - similar liquid in appearance - nursing/pharmacy/medical staff will be blinded. Both formulations - sucrose, glycerol, flavouring and purified water so will be identical in taste (melatonin added to intervention formulation)


Outcome: Delirium free assessments (as measured by CAM-ICU score)
Timepoint: Twice daily assessment - percentage of delirium free assessments during ICU stay or 14 days (whichever is shorter)

Data Dictionary: Not Available

Will individual participant data (IPD) for this trial be available?


What data in particular will be shared?

outcome data

When will data be available?

post publication start date - once accepted for publication - expect 2020 end date- no end date determined

Available to whom?

any researcher on permission of authors

Available for what types of analyses?

any purpose - not currently limited to certain type of analyses - again on permission of authors

Source study information is derived from the Australian New Zealand Clinical Trials Registry (ANZCTR). For more information on the ANZCTR, please see