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

Sponsor

Ciusss de L'Est de l'Île de Montréal (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05713877

Collaborator

Maisonneuve-Rosemont Hospital (Other)

Enrollment

Location

Arms

9.9

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Delirium	Drug: Melatonin Drug: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes 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.

Primary Purpose:

Treatment

Official Title:

DELIRE-ICU: A Randomised Controlled Feasibility Trial of Melatonin vs Placebo in the Treatment of Delirium in the Intensive Care Unit

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Sep 30, 2023

Anticipated Study Completion Date :

Nov 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: 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.
Placebo Comparator: Enteral placebo ORA-BLEND SF® (sugar-free flavoured suspending vehicle). Final volume in the oral syringe will be 9 mL.	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.

Arm

Intervention/Treatment

Experimental: 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.

Drug: 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.

Placebo Comparator: Enteral placebo

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

Drug: Placebo

Outcome Measures

Primary Outcome Measures

Feasibility: Enrollment rate [8 months]
Average enrollment rate of participants per month.
Clinical: Duration of delirium [14 days]
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 [8 months]
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 [8 months]
Proportion of participants recruited among eligible patients.
Clinical: Adverse events [14 days]
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.

Other Outcome Measures

Feasibility: Completion of study [8 months]
Proportion of participants who completed the study and reasons associated with withdrawal.
Feasibility: MDAS assessment time (minutes) [8 months]
Time required for the administration of the Memorial Delirium Assessment Scale (MDAS). Values from 0 to 30. A higher score means a worse outcome.
Feasibility: Completion of ICDSC [8 months]
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.
Clinical: Antipsychotics dose (mg) administered to participants [14 days]
Cumulative dose of de novo antipsychotics, reported in haloperidol equivalent dose, received by participants during delirium.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hopital Maisonneuve-Rosemont	Montréal	Quebec	Canada	H1T 2M4

Sponsors and Collaborators

Ciusss de L'Est de l'Île de Montréal
Maisonneuve-Rosemont Hospital

Investigators

Principal Investigator: François Marquis, M.D., M.A., Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Est-de-l'Île-de-Montréal