search
Back to results

Melatonin for Treatment of Delirium in Critically Ill Adult Patients (DELIRE-ICU)

Primary Purpose

Delirium

Status
Recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Melatonin
Placebo
Sponsored by
Ciusss de L'Est de l'Île de Montréal
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Delirium focused on measuring Melatonin, Intensive care, Feasibility, Treatment, Critically ill, ICU

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hopital Maisonneuve-RosemontRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Enteral melatonin 9 mg

Enteral placebo

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Feasibility: Enrollment rate
Average enrollment rate of participants per month.
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.

Secondary Outcome Measures

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.
Feasibility: Consent rate
Proportion of participants recruited among eligible patients.
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.

Full Information

First Posted
January 26, 2023
Last Updated
February 23, 2023
Sponsor
Ciusss de L'Est de l'Île de Montréal
Collaborators
Maisonneuve-Rosemont Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT05713877
Brief Title
Melatonin for Treatment of Delirium in Critically Ill Adult Patients
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2023 (Actual)
Primary Completion Date
September 30, 2023 (Anticipated)
Study Completion Date
November 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ciusss de L'Est de l'Île de Montréal
Collaborators
Maisonneuve-Rosemont Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Delirium
Keywords
Melatonin, Intensive care, Feasibility, Treatment, Critically ill, ICU

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
All study personnel, care provider, patients and their families will remain blinded. Randomization will be performed by members of the Pharmacy Research Department.
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Enteral melatonin 9 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Enteral placebo
Arm Type
Placebo Comparator
Arm Description
ORA-BLEND SF® (sugar-free flavoured suspending vehicle). Final volume in the oral syringe will be 9 mL.
Intervention Type
Drug
Intervention Name(s)
Melatonin
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Feasibility: Enrollment rate
Description
Average enrollment rate of participants per month.
Time Frame
8 months
Title
Clinical: Duration of delirium
Description
Compare the average duration of an episode of delirium defined as the number of days with ICDSC score ≥4 between the 2 groups.
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Feasibility: Study adherence
Description
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.
Time Frame
8 months
Title
Feasibility: Consent rate
Description
Proportion of participants recruited among eligible patients.
Time Frame
8 months
Title
Clinical: Adverse events
Description
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.
Time Frame
14 days
Other Pre-specified Outcome Measures:
Title
Feasibility: Completion of study
Description
Proportion of participants who completed the study and reasons associated with withdrawal.
Time Frame
8 months
Title
Feasibility: MDAS assessment time (minutes)
Description
Time required for the administration of the Memorial Delirium Assessment Scale (MDAS). Values from 0 to 30. A higher score means a worse outcome.
Time Frame
8 months
Title
Feasibility: Completion of ICDSC
Description
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.
Time Frame
8 months
Title
Clinical: Antipsychotics dose (mg) administered to participants
Description
Cumulative dose of de novo antipsychotics, reported in haloperidol equivalent dose, received by participants during delirium.
Time Frame
14 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Johannie Beaucage-Charron, Pharm.D., M.Sc.
Phone
514 252 3400
Ext
6125
Email
johannie.beaucage-charron.cemtl@ssss.gouv.qc.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
François Marquis, M.D., M.A.
Organizational Affiliation
Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Est-de-l'Île-de-Montréal
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital Maisonneuve-Rosemont
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Johannie Beaucage-Charron, Pharm.D., M.Sc.
First Name & Middle Initial & Last Name & Degree
Katerine Chalifoux, Pharm.D.
First Name & Middle Initial & Last Name & Degree
Marianne Leblanc, Pharm.D.
First Name & Middle Initial & Last Name & Degree
Mounia Louerguioui, Pharm.D.
First Name & Middle Initial & Last Name & Degree
Patricia Poirier, Pharm.D.
First Name & Middle Initial & Last Name & Degree
Aryane Roy, B.Pharm.
First Name & Middle Initial & Last Name & Degree
Winnie Tran, Pharm.D.

12. IPD Sharing Statement

Citations:
PubMed Identifier
10411009
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.
Results Reference
background
PubMed Identifier
19588122
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.
Results Reference
background
PubMed Identifier
34401939
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.
Results Reference
background
PubMed Identifier
33730927
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.
Results Reference
background
PubMed Identifier
20053301
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.
Results Reference
background
PubMed Identifier
32837850
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.
Results Reference
background
PubMed Identifier
28363933
Citation
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.
Results Reference
background
PubMed Identifier
20053272
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.
Results Reference
background

Learn more about this trial

Melatonin for Treatment of Delirium in Critically Ill Adult Patients

We'll reach out to this number within 24 hrs