title: Feasibility of melatonin for prevention of delirium in critically ill patients: a protocol for a multicentre, randomised, placebo-controlled study.
abstract: Delirium is highly prevalent in the intensive care unit (ICU) and is associated with adverse clinical outcomes. At this time, there is no drug that effectively prevents delirium in critically ill patients. Alterations in melatonin secretion and metabolism may contribute to the development of delirium. Administration of exogenous melatonin has been shown to prevent delirium in non-critically ill surgical and medical patients. This trial will demonstrate the feasibility of a planned multicentre, randomised controlled trial to test the hypothesis that melatonin can prevent delirium in critically ill patients compared with placebo.
  
  
  
  This feasibility trial is a randomised, 3-arm, placebo-controlled study of melatonin (2 vs 0.5 mg vs placebo, administered for a maximum of 14 days) for the prevention of delirium in critically ill patients. A total of 69 patients aged 18 years and older with an expected ICU length of stay >48 hours will be recruited from 3 Canadian ICUs. The primary outcome is protocol adherence (ie, overall proportion of study drug doses administered in the prescribed administration window). Secondary outcomes include pharmacokinetic parameters, incidence, time to onset, duration of delirium, number of delirium-free days, adverse events, self-reported sleep quality, rest-activity cycles measured by wrist actigraphy, duration of mechanical ventilation, ICU length of stay and mortality. Data will be analysed using an intention-to-treat approach.
  
  
  
  The study has been approved by Health Canada and the research ethics board of each study site. Trial results will be presented at international conferences and published in a peer-reviewed journal.
  
  
  
  NCT02615340: Pre-results.
authors.affiliation: Department of Pharmacy, Mount Sinai Hospital, and Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Burry
authors.affiliation: Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, and Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada.
authors.forename: Damon
authors.initials: D
authors.lastname: Scales
authors.affiliation: Department of Pharmacy, Hôpital du Sacré-Coeur de Montréal, and Faculté de pharmacie, Université de Montréal, Montréal, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Williamson
authors.affiliation: Department of Critical Care, IWK Health Centre, and Dalhousie University, Halifax, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Foster
authors.affiliation: Department of Medicine and Interdepartmental Division of Critical Care Medicine, Mount Sinai Hospital and University of Toronto, Toronto, Canada.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Mehta
authors.affiliation: Department of Pharmacy, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Guenette
authors.affiliation: Interdepartmental Division of Critical Care Medicine and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.
authors.forename: Eddy
authors.initials: E
authors.lastname: Fan
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario, Canada.|Department of Medicine, University of Toronto and Department of Medicine, Mount Sinai Hospital, Toronto, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Detsky
authors.affiliation: Mount Sinai Services, Mount Sinai Hospital, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
authors.forename: Azar
authors.initials: A
authors.lastname: Azad
authors.affiliation: Département de Médecine, Hôpital du Sacré-Cœur de Montréal, and Département de Médecine, Université de Montréal, Montreal, Canada.|Département de Médecine, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Francis
authors.initials: F
authors.lastname: Bernard
authors.affiliation: Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, and Lawrence S. Bloomberg Faculty of Nursing and Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada.
authors.forename: Louise
authors.initials: L
authors.lastname: Rose
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002492:Central Nervous System Depressants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016638:Critical Illness; D003693:Delirium / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008550:Melatonin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged; D018579:Patient Selection; D010865:Pilot Projects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D002492:Central Nervous System Depressants; D008550:Melatonin
keywords: INTENSIVE & CRITICAL CARE; melatonin