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Recruiting NCT05713877

Melatonin for Treatment of Delirium in Critically Ill Adult Patients

Phase II Interventional Delirium

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Melatonin, Placebo.
Who it may be relevant to
Registry conditions: Delirium. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Canada
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

DELIRE-ICU: A Randomised Controlled Feasibility Trial of Melatonin vs Placebo in the Treatment of Delirium in the Intensive Care Unit

Overview

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.

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.

Interventions

  • Drug Melatonin
    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.
  • Drug Placebo
    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.

Primary outcome measures

  • Feasibility: Enrollment rate [Time frame: 8 months]
  • Clinical: Duration of delirium [Time frame: 14 days]
Secondary outcome measures (3)
  • Feasibility: Study adherence [Time frame: 8 months]
  • Feasibility: Consent rate [Time frame: 8 months]
  • Clinical: Adverse events [Time frame: 14 days]

Eligibility criteria

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

  • 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Quadruple blind
Primary purpose
Treatment

Study locations

Canada · 1 center
  • Hopital Maisonneuve-Rosemont — Montreal

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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 20053272

Identifiers

NCT: NCT05713877 · 2023-3247

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗