Melatonin for Prevention of Delirium in Critically Ill Patients

NCT02615340 | Unknown Phase 2

• 1 other identifier: 4000145150
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to determine the feasibility of conducting a randomized controlled trial (RCT) with melatonin for prevention of delirium in critically ill adult patients. The investigators hypothesize that melatonin, administered on a scheduled nightly basis during ICU admission, will be efficacious and safe for the prevention of delirium in critically ill adults.

Conditions

Delirium

Keywords

delirium; melatonin; pharmacokinetics; feasibility; prevention

Outcome Measures

Primary Outcomes (1)

• Feasibility: Study adherence

  Investigators will calculate protocol adherence as the overall proportion of administered doses in the prescribed dose administration window (between 21:00 and to 23:59 hours) divided by total number of eligible study days.

  1 year

Secondary Outcomes (18)

• Feasibility: Trial recruitment

  1 year

• Feasibility: Time in motion (minutes)

  1 year

• Pharmacokinetic: Peak melatonin concentration (Cmax)

  24 hours

• Pharmacokinetic: Time of peak melatonin concentration (Tmax)

  24 hours

• Pharmacokinetic: Morning melatonin concentration (C9AM)

  24 hours

Study Arms (3)

Enteral melatonin 0.5 mg

ACTIVE COMPARATOR

Melatonin 0.5 mg from the 1mg/mL oral suspension qs to 5 mL with Oral Mix SF (sugar-free flavoured suspending vehicle) (final concentration of 0.1 mg/mL; final volume in the oral syringe will be 5 mL)

Drug: Melatonin

Enteral melatonin 2 mg

ACTIVE COMPARATOR

Melatonin 2 mg from the 1mg/mL oral suspension qs to 5 mL with Oral Mix SF (sugar-free flavoured suspending vehicle) (final concentration 0.4 mg/mL; final volume in the oral syringe will be 5 mL)

Drug: Melatonin

Enteral matched placebo

PLACEBO COMPARATOR

Melatonin 0 mg qs to 5 mL with Oral Mix SF (sugar-free flavoured suspending vehicle) (final concentration 0 mg/mL; final volume in the oral syringe will be 5 mL)

Drug: Placebo

Interventions

Melatonin DRUG

Study drug will be given at 21:00 - 23:59 daily, starting on the day of enrolment until ICU discharge, death, or up to 14 days, as most critically ill patients are at greatest risk of delirium in the first two weeks of admission. The study medication will be given by mouth (PO or per os) or if needed, via the feeding tube followed by a flush with 20mL water. Doses can be given up to midnight if administration needs to be delayed for procedures or investigations.

Also known as: N-acetyl-5-methoxytryptamine

Enteral melatonin 0.5 mg; Enteral melatonin 2 mg

Placebo DRUG

Study drug will be given at 21:00 - 23:59 daily, starting on the day of enrolment until ICU discharge, death, or up to 14 days, as most critically ill patients are at greatest risk of delirium in the first two weeks of admission. The study medication will be given by mouth (PO or per os) or if needed, via the feeding tube followed by a flush with 20mL water. Doses can be given up to midnight if administration needs to be delayed for procedures or investigations.

Enteral matched placebo

Eligibility Criteria

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

You may qualify if:

• Critically ill patients ≥18 years of age
• Anticipated ICU stay of \>48 hours
• Able to receive enteral administration of study drug (i.e. by mouth or any feeding tube = naso- or oro- or percutaneous gastric or post-pyloric feeding tube)
• Consent to participate.

You may not qualify if:

• ICU admission of \>48 hours prior to screening
• Unable to assess for delirium (e.g. comatose defined as SAS 1 or 2 or either 'No Response' Score A or B on ICDSC, chemically paralyzed with neuromuscular blocking drugs)
• Screened delirium positive prior to randomization (ICDSC score ≥4 out of 8)
• Anticipated withdrawal in next 48 hours
• Known history of severe cognitive or neurodegenerative disease (e.g. dementia, Parkinson's disease) or severe structural brain injury (e.g. traumatic brain injury, intracranial hemorrhage) as the ICDSC assessment tool has not been validated in these patient populations
• Unable to communicate in English or French (Montreal site)
• Contraindications to receiving any enteral medication (defined as absolute contraindication to enteral nutrition such as gastrointestinal obstruction, perforation, recent upper GI surgery, no enteral access)
• Active seizures
• Known pregnancy
• Legal blindness
• Known allergy to melatonin

Sponsors & Collaborators

• Mount Sinai Hospital, Canada: lead
• Sunnybrook Health Sciences Centre: collaborator
• Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal: collaborator

Study Sites (3)

Mount Sinai Hospital

Toronto, Ontario, M5G1X5, Canada

RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

RECRUITING

Hôpital du Sacré-Coeur

Montreal, Quebec, Canada

NOT YET RECRUITING

Related Publications (2)

• Burry LD, Williamson DR, Detsky ME, Bernard F, Foster J, Mehta S, Pinto R, Scales DC, Rose L. Low-Dose Melatonin for Prevention of Delirium in Critically Ill Patients: A Multicenter, Randomized, Placebo-Controlled Feasibility Trial. Chest. 2025 May;167(5):1397-1407. doi: 10.1016/j.chest.2024.12.030. Epub 2025 Jan 10.

  PMID: 39800236 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Delirium

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Lisa Burry, PharmD

  MOUNT SINAI HOSPITAL

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lisa Burry, PharmD

CONTACT

4165864800; lisa.burry@sinaihealthsystem.ca

Louise Rose

CONTACT

416978-3492; louise.rose@utoronto.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, patients, and their families will remain blinded. Treatment allocation will only be known to the clinical trials pharmacist, who will perform subject randomization.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2015
• First Posted: November 26, 2015
• Study Start: October 12, 2017
• Primary Completion: October 12, 2018
• Study Completion: October 12, 2019
• Last Updated: October 19, 2017

Record last verified: 2017-10

Locations

CA (3)