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  • Feasibility of melatonin for prevention of delirium in critically ill patients: a protocol for a multicentre, randomised, placebo-controlled study

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Intensive care
Protocol
Feasibility of melatonin for prevention of delirium in critically ill patients: a protocol for a multicentre, randomised, placebo-controlled study
  1. Lisa Burry1,
  2. Damon Scales2,
  3. David Williamson3,
  4. Jennifer Foster4,
  5. Sangeeta Mehta5,
  6. Melanie Guenette6,
  7. Eddy Fan7,
  8. Michael Detsky8,9,
  9. Azar Azad10,
  10. Francis Bernard11,12,
  11. Louise Rose13
  1. 1Department of Pharmacy, Mount Sinai Hospital, and Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada
  2. 2Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, and Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada
  3. 3Department of Pharmacy, Hôpital du Sacré-Coeur de Montréal, and Faculté de pharmacie, Université de Montréal, Montréal, Canada
  4. 4Department of Critical Care, IWK Health Centre, and Dalhousie University, Halifax, Canada
  5. 5Department of Medicine and Interdepartmental Division of Critical Care Medicine, Mount Sinai Hospital and University of Toronto, Toronto, Canada
  6. 6Department of Pharmacy, Mount Sinai Hospital, Toronto, Ontario, Canada
  7. 7Interdepartmental Division of Critical Care Medicine and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
  8. 8Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  9. 9Department of Medicine, University of Toronto and Department of Medicine, Mount Sinai Hospital, Toronto, Canada
  10. 10Mount Sinai Services, Mount Sinai Hospital, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
  11. 11Département de Médecine, Hôpital du Sacré-Cœur de Montréal, and Département de Médecine, Université de Montréal, Montreal, Canada
  12. 12Département de Médecine, Université de Montréal, Montreal, Quebec, Canada
  13. 13Department 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
  1. Correspondence to Dr Lisa Burry; lisa.burry{at}sinaihealthsystem.ca

Abstract

Introduction 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.

Methods and analysis 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.

Ethics and dissemination 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.

Trial registration number NCT02615340: Pre-results.

  • INTENSIVE & CRITICAL CARE
  • melatonin

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/bmjopen-2016-015420

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    Footnotes

    • Contributors LB, DS, DW, JF, SM, MG, EF, MD, AA, FB and LR made substantial contributions to the conception and/or design of the study protocol. LB, DS, DW and LR conceived of the overall study and wrote the first draft of the protocol and this manuscript. LB, DS, DW, AA and LR provided critical input pertaining to the design of the study interventions, procedures and outcomes. LB, DS, MG, AA and LR designed the data analysis and management plan. LB, DS, DW, JF, SM, EF, MD, FB and LR critically revised the protocol for important intellectual content and approved the final version to be published. LB, DS, DW, JF, SM, MG, EF, MD, AA, FB and LR agree to be accountable for all aspects of the work, ensuring its accuracy and integrity.

    • Funding This work was supported by the Centre for Collaborative Drug Research at the University of Toronto (Pilot Project Fund 2015).

    • Competing interests None declared.

    • Ethics approval Health Canada (No Objection Letter, #197507, 7 November 2016) and the research ethics board of each participating centre have approved the protocol (Sunnybrook Health Sciences Centre #086-2016; Mount Sinai Hospital #16-0097-A and Hôpital du Sacré-Coeur de Montréal #2017-1385).

    • Provenance and peer review Not commissioned; externally peer reviewed.