Melatonin for Treatment of Delirium in Critically Ill Adult Patients

Delirium Clinical Trial

— DELIRE-ICU  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05713877
• Other study ID #: 2023-3247
• Status: Recruiting
• Phase: Phase 2
• Start date: February 1, 2023
• Est. completion date: November 30, 2024

Study information

• Verified date: February 2024
• Source: Ciusss de L'Est de l'Île de Montréal
• Contact: Johannie Beaucage-Charron, Pharm.D., M.Sc.
• Phone: 514 252 3400
• Email: johannie.beaucage-charron.cemtl[@]ssss.gouv.qc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: November 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Delirium

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	Hopital Maisonneuve-Rosemont	Montréal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Ciusss de L'Est de l'Île de Montréal	Maisonneuve-Rosemont Hospital

Country where clinical trial is conducted

Canada, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. Erratum In: J Gerontol A Biol Sci Med Sci 1999 Jul;54(7):B275. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: BMC Med Res Methodol. 2023 Mar 11;23(1):59. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Feasibility: Completion of study	Proportion of participants who completed the study and reasons associated with withdrawal.	8 months
Other	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.	8 months
Other	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.	8 months
Other	Clinical: Antipsychotics dose (mg) administered to participants	Cumulative dose of de novo antipsychotics, reported in haloperidol equivalent dose, received by participants during delirium.	14 days
Primary	Feasibility: Enrollment rate	Average enrollment rate of participants per month.	8 months
Primary	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.	14 days
Secondary	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.	8 months
Secondary	Feasibility: Consent rate	Proportion of participants recruited among eligible patients.	8 months
Secondary	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.	14 days