Melatonin for Prevention of Delirium in Critically Ill Patients

NCT ID: NCT02615340

Last Updated: 2017-10-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-12
• Study Completion Date: 2019-10-12

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.

Detailed Description

The available evidence indicates melatonin may decrease the incidence of delirium in non-critically ill patient populations; however, trials in the critically ill are lacking. 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. The null hypothesis is that there is no difference in delirium incidence between placebo and melatonin. Prior to conducting an adequately powered multi-centre, blinded randomized, placebo-controlled trial in critically ill patients, there is a need for a better understanding of melatonin pharmacokinetics (PK) in critically ill patients. This will help to determine appropriate dosing, drug administration issues (specifically protocol adherence), adverse drug effects, and recruitment rates based on inclusion and exclusion criteria.

The specific aim is to conduct a phase II triple blind, placebo-controlled randomized trial comparing two doses of melatonin (low dose = 0.5 mg and high dose = 2.0 mg) to assess the feasibility of a future full-scale RCT. Feasibility of the larger trial will be based on protocol adherence and participant recruitment rates. Data on PK properties of melatonin will be assessed to determine dosing for future studies of melatonin for delirium prevention in the critically ill.

Conditions

Delirium

Keywords

delirium; melatonin; pharmacokinetics; feasibility; prevention

Study Design

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

Study Groups

Enteral melatonin 0.5 mg

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)

Group Type: ACTIVE_COMPARATOR

Melatonin

Intervention Type: 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 melatonin 2 mg

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)

Group Type: ACTIVE_COMPARATOR

Melatonin

Intervention Type: 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

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)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Interventions

Melatonin

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Other Intervention Names

N-acetyl-5-methoxytryptamine

Eligibility Criteria

Inclusion Criteria

1. Critically ill patients ≥18 years of age

2. Anticipated ICU stay of >48 hours

3. 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)

4. Consent to participate.

Exclusion Criteria

1. ICU admission of >48 hours prior to screening

2. 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)

3. Screened delirium positive prior to randomization (ICDSC score ≥4 out of 8)

4. Anticipated withdrawal in next 48 hours

5. 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

6. Unable to communicate in English or French (Montreal site)

7. 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)

8. Active seizures

9. Known pregnancy

10. Legal blindness

11. Known allergy to melatonin

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

Sponsors

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role: collaborator

Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal

OTHER

Sponsor Role: collaborator

Mount Sinai Hospital, Canada

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lisa Burry, PharmD

Role: PRINCIPAL_INVESTIGATOR

MOUNT SINAI HOSPITAL

Locations

Mount Sinai Hospital

Toronto, Ontario, Canada

Site Status: RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status: RECRUITING

Hôpital du Sacré-Coeur

Montreal, Quebec, Canada

Site Status: NOT_YET_RECRUITING

Countries

Canada

Central Contacts

Lisa Burry, PharmD

Role: CONTACT

Phone: 4165864800

Email: lisa.burry@sinaihealthsystem.ca

Louise Rose

Role: CONTACT

Phone: 416978-3492

Email: louise.rose@utoronto.ca

Facility Contacts

Lisa Burry, PharmD

Role: primary

Damon Scales

Role: primary

David Williamson

Role: primary

References

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.

Reference Type: DERIVED

PMID: 39800236 (View on PubMed)

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: DERIVED

PMID: 28363933 (View on PubMed)

Other Identifiers

4000145150

Identifier Type: -

Identifier Source: org_study_id