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)

Funding

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 .... 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 days and use of anti-psychotics, sedatives and physical restraints. The economic analysis will evaluate the cost benefits of the intervention Participant recruitment 850 patients from Adult Public ICUs who meet all of the inclusion and none of the exclusion criteria. Randomisation and enrolment will only occur Monday-Friday due to limitation of resources although treatment and assessment will occur on weekends and after-hours. Randomisation and consent Patients may be unable to consent at time of enrolment. In these cases an emergency waiver of consent will be used, as allowed for in the NHMRC National Statement, in conjunction with acknowledgement from the patient’s next-of-kin that they are not aware of any reason why the patient would have chosen not to participate. All patients will be followed up and provided the opportunity to consent to continued study participation once capacity is regained. Intervention Melatonin 4mg in oral suspension or placebo (similar appearance) will be given at 21:00 for 14 days or until discharge from ICU. A subset of 100 patients will have two separate sleep EEGs done which is the gold standard to assess sleep quality and duration on days 2-3 and 5-7 of their admission Analysis described earlier. An interim analysis will take place after 100 patients and 400 patients (employing peto-haybittle rule with p value 0.001) and a pre-planned economic analysis Outcome assessment will be done by trained intensive care registrars. Data recording and management will be done by the principal investigators and research nurses
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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 .... 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 affect their ability to participate in a CAM-ICU assessment (as judged by treating physician) 8 No enteral route – melatonin not available in intravenous formulation 9 Pregnancy or breastfeeding. 10. Hepatic impairment defined as Alanine Transferase (ALT) >500 IU/L, previous liver transplant or liver cirrhosis categories Childs-Pugh B and C.
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