Melatonin for Treatment of Delirium in Critically Ill Adult Patients

NCT ID: NCT05713877

Last Updated: 2025-02-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-01
• Study Completion Date: 2025-12-30

Brief 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.

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.

Conditions

Delirium

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Melatonin

Intervention Type: DRUG

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.

Enteral placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Maisonneuve-Rosemont Hospital

OTHER

Sponsor Role: collaborator

Ciusss de L'Est de l'Île de Montréal

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

François Marquis, M.D., M.A.

Role: PRINCIPAL_INVESTIGATOR

Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Est-de-l'Île-de-Montréal

Locations

Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Johannie Beaucage-Charron, Pharm.D., M.Sc.

Role: CONTACT

johannie.beaucage-charron.cemtl@ssss.gouv.qc.ca

514 252 3400 ext. 6125

Facility Contacts

Johannie Beaucage-Charron, Pharm.D., M.Sc.

Role: primary

References

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.

Reference Type: BACKGROUND

PMID: 10411009 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19588122 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34401939 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33730927 (View on PubMed)

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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

PMID: 28363933 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20053272 (View on PubMed)

Other Identifiers

2023-3247

Identifier Type: -

Identifier Source: org_study_id