Melatonin for Treatment of Delirium in Critically Ill Adult Patients

NCT05713877 | Recruiting Phase 2

• 1 other identifier: 2023-3247
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Delirium

Keywords

Melatonin; Intensive care; Feasibility; Treatment; Critically ill; ICU

Outcome Measures

Primary Outcomes (2)

• Feasibility: Enrollment rate

  Average enrollment rate of participants per month.

  8 months

• 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 Outcomes (3)

• Feasibility: Study adherence

  8 months

• Feasibility: Consent rate

  8 months

• Clinical: Adverse events

  14 days

Other Outcomes (4)

• Feasibility: Completion of study

  8 months

• Feasibility: MDAS assessment time (minutes)

  8 months

• Feasibility: Completion of ICDSC

  8 months

Study Arms (2)

Enteral melatonin 9 mg

EXPERIMENTAL

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

Enteral placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Melatonin 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 melatonin 9 mg

Placebo 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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ciusss de L'Est de l'Île de Montréal: lead
• Maisonneuve-Rosemont Hospital: collaborator

Study Sites (1)

Hopital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

RECRUITING

Related Publications (8)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Delirium; Critical Illness

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• François Marquis, M.D., M.A.

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

CONTACT

514 252 3400; johannie.beaucage-charron.cemtl@ssss.gouv.qc.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All study personnel, care provider, patients and their families will remain blinded. Randomization will be performed by members of the Pharmacy Research Department.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2023
• First Posted: February 6, 2023
• Study Start: February 1, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: March 23, 2026

Record last verified: 2026-02

Locations

CA (1)