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RecruitingNCT05713877DELIRE-ICUUpdated Mar 23, 2026

Melatonin for Treatment of Delirium in Critically Ill Adult Patients

A Phase 2 interventional study of Melatonin and Placebo in Delirium, sponsored by Ciusss de L'Est de l'Île de Montréal. Recruiting at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-23.

Sponsored by Ciusss de L'Est de l'Île de Montréal · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
30
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to determine the feasibility of conducting a randomized controlled trial (RCT) with melatonin for treatment of delirium in critically ill adult patients. From a feasibility perspective, the investigators believe that the proposed design will achieve the minimum enrollment rate necessary to conduct a future RCT on a larger scale.

Read the detailed description

The prevalence of delirium is high in the intensive care unit (ICU), yet there is no pharmacological treatment that has been proven effective. The investigators hypothesize that melatonin, given on a daily basis at 21:00, will safely decrease the mean duration of a delirium episode in ICU patients. The current literature evaluating melatonin as a treatment for delirium is lacking, therefore more studies are needed.

It is estimated that an alteration of sleep pattern can be found in up to 75% of patients with delirium. This raises the hypothesis that prevention and treatment of sleep disorders could potentially improve delirium. Sleep and circadian rhythm disturbances are associated with low endogenous melatonin secretion and studies have shown that it also occurs in patients with delirium.

Thus, the objective is to conduct a phase II double blind, placebo-controlled randomized trial comparing melatonin 9 mg to placebo to evaluate the feasibility of a future large-scale RCT. Participants will be followed during their stay in the ICU and after their transfer on another unit up to a maximum of 14 days. Feasibility of the larger trial will mainly be based on enrollment rates.

02

Conditions studied

  • Delirium

Keywords

  • Melatonin
  • Intensive care
  • Feasibility
  • Treatment
  • Critically ill
  • ICU
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patients aged 18 years or older admitted to the intensive care unit;
  • Anticipated ICU stay > 48 hours;
  • ICDSC score greater than or equal to 4 for a maximum of 48 hours prior to randomization.

Exclusion criteria

Exclusion Criteria:

  • Known allergy or hypersensitivity to melatonin or to ingredients in ORA-BLEND SF®;
  • Use of melatonin within 24 hours prior to randomization;
  • Presence of severe structural brain injury (intracranial hemorrhage or traumatic brain injury), severe major neurocognitive disorder, advanced neurodegenerative disease or hepatic encephalopathy;
  • Diagnosis of schizophrenia, bipolar affective disorder, psychotic depression, uremic encephalopathy or alcohol withdrawal;
  • Presence of active seizures, coma, aphasia or severe intellectual disability;
  • Limited short-term vital prognosis;
  • Diagnosis of delirium prior to ICU admission;
  • Pregnancy or breastfeeding;
  • Absolute contraindication to receive enteral medication;
  • Inability to understand or speak English or French;
  • Total blindness.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
30 participants (estimated)

Study arms

  • Experimental
    Enteral melatonin 9 mg

    Melatonin 9 mg from a 1 mg/mL oral suspension of melatonin in ORA-BLEND SF® (sugar-free flavoured suspending vehicle). Final volume in the oral syringe will be 9 mL.

    Drug: Melatonin

  • Placebo comparator
    Enteral placebo

    ORA-BLEND SF® (sugar-free flavoured suspending vehicle). Final volume in the oral syringe will be 9 mL.

    Drug: Placebo

Interventions

  • DrugMelatonin

    Study drug will be given at 21:00 daily, starting on the day of enrolment until delirium resolution, hospital discharge, death, or up to 14 days. The study medication will be given by mouth (PO or per os) or, if needed, via the feeding tube.

  • DrugPlacebo

    Study drug will be given at 21:00 daily, starting on the day of enrolment until delirium resolution, hospital discharge, death, or up to 14 days. The study medication will be given by mouth (PO or per os) or, if needed, via the feeding tube.

05

What researchers measure

Primary outcomes

  1. Feasibility: Enrollment rate

    Average enrollment rate of participants per month.

    Time frame: 8 months

  2. Clinical: Duration of delirium

    Compare the average duration of an episode of delirium defined as the number of days with ICDSC score ≥4 between the 2 groups.

    Time frame: 14 days

Secondary outcomes

  1. Feasibility: Study adherence

    Proportion of administered doses in the prescribed dose administration window (between 19:00 and 23:00 hours) divided by total number of eligible study days.

    Time frame: 8 months

  2. Feasibility: Consent rate

    Proportion of participants recruited among eligible patients.

    Time frame: 8 months

  3. Clinical: Adverse events

    Incidence of adverse events reported in the Canadian melatonin monograph (i.e. headache and nausea) observed by the investigators or reported by the treating team.

    Time frame: 14 days

Other outcomes

  1. Feasibility: Completion of study

    Proportion of participants who completed the study and reasons associated with withdrawal.

    Time frame: 8 months

  2. Feasibility: MDAS assessment time (minutes)

    Time required for the administration of the Memorial Delirium Assessment Scale (MDAS). Values from 0 to 30. A higher score means a worse outcome.

    Time frame: 8 months

  3. Feasibility: Completion of ICDSC

    Proportion of missing data in the completion of the Intensive Care Delirium Screening Checklist (ICDSC). Values from 0 to 8. A higher score means a worse outcome.

    Time frame: 8 months

  4. Clinical: Antipsychotics dose (mg) administered to participants

    Cumulative dose of de novo antipsychotics, reported in haloperidol equivalent dose, received by participants during delirium.

    Time frame: 14 days

06

Study locations

1 of 1 sites recruiting
  • Hopital Maisonneuve-Rosemont
    Montreal, Quebec H1T 2M4, Canada
    • Johannie Beaucage-Charron, Pharm.D., M.Sc. · Contact
    • Katerine Chalifoux, Pharm.D. · Sub investigator
    • Marianne Leblanc, Pharm.D. · Sub investigator
    • Mounia Louerguioui, Pharm.D. · Sub investigator
    • Patricia Poirier, Pharm.D. · Sub investigator
    • Aryane Roy, B.Pharm. · Sub investigator
    • Winnie Tran, Pharm.D. · Sub investigator
    Recruiting
07

References and documents

Publications

  • Flacker JM, Lipsitz LA. Neural mechanisms of delirium: current hypotheses and evolving concepts. J Gerontol A Biol Sci Med Sci. 1999 Jun;54(6):B239-46. doi: 10.1093/gerona/54.6.b239. PubMed 10411009 ↗
  • Pandharipande PP, Morandi A, Adams JR, Girard TD, Thompson JL, Shintani AK, Ely EW. Plasma tryptophan and tyrosine levels are independent risk factors for delirium in critically ill patients. Intensive Care Med. 2009 Nov;35(11):1886-92. doi: 10.1007/s00134-009-1573-6. Epub 2009 Jul 9. PubMed 19588122 ↗
  • Stollings JL, Kotfis K, Chanques G, Pun BT, Pandharipande PP, Ely EW. Delirium in critical illness: clinical manifestations, outcomes, and management. Intensive Care Med. 2021 Oct;47(10):1089-1103. doi: 10.1007/s00134-021-06503-1. Epub 2021 Aug 16. PubMed 34401939 ↗
  • Sun T, Sun Y, Huang X, Liu J, Yang J, Zhang K, Kong G, Han F, Hao D, Wang X. Sleep and circadian rhythm disturbances in intensive care unit (ICU)-acquired delirium: a case-control study. J Int Med Res. 2021 Mar;49(3):300060521990502. doi: 10.1177/0300060521990502. PubMed 33730927 ↗
  • Weinhouse GL, Schwab RJ, Watson PL, Patil N, Vaccaro B, Pandharipande P, Ely EW. Bench-to-bedside review: delirium in ICU patients - importance of sleep deprivation. Crit Care. 2009;13(6):234. doi: 10.1186/cc8131. Epub 2009 Dec 7. PubMed 20053301 ↗
  • Farasat S, Dorsch JJ, Pearce AK, Moore AA, Martin JL, Malhotra A, Kamdar BB. Sleep and Delirium in Older Adults. Curr Sleep Med Rep. 2020;6(3):136-148. doi: 10.1007/s40675-020-00174-y. Epub 2020 Jul 27. PubMed 32837850 ↗
  • Burry L, Scales D, Williamson D, Foster J, Mehta S, Guenette M, Fan E, Detsky M, Azad A, Bernard F, Rose L. Feasibility of melatonin for prevention of delirium in critically ill patients: a protocol for a multicentre, randomised, placebo-controlled study. BMJ Open. 2017 Mar 30;7(3):e015420. doi: 10.1136/bmjopen-2016-015420. PubMed 28363933 ↗
  • Thabane L, Ma J, Chu R, Cheng J, Ismaila A, Rios LP, Robson R, Thabane M, Giangregorio L, Goldsmith CH. A tutorial on pilot studies: the what, why and how. BMC Med Res Methodol. 2010 Jan 6;10:1. doi: 10.1186/1471-2288-10-1. PubMed 20053272 ↗
08

Registry details

Key details

Study ID
NCT05713877
Lead sponsor
Ciusss de L'Est de l'Île de Montréal
Collaborators
Maisonneuve-Rosemont Hospital
Responsible party
Sponsor
First posted
Feb 6, 2023
Start date
Feb 1, 2023
Primary completion
Dec 30, 2026 (estimated)
Completion
Dec 30, 2026 (estimated)
Last update
Mar 23, 2026

Study contacts

Johannie Beaucage-Charron, Pharm.D., M.Sc.
Contact
johannie.beaucage-charron.cemtl@ssss.gouv.qc.ca
514 252 3400 ext. 6125
François Marquis, M.D., M.A.
principal investigator · Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Est-de-l'Île-de-Montréal

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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