Prevention of Delirium in Intensive Care by Melatonin

Phase 2

Completed

• Conditions: Mechanically Ventilated Patients
• Interventions: Drug: PLACEBO; Drug: MELATONIN (HIGH DOSE); Drug: MELATONIN (LOW DOSE)

• Registration Number: NCT03524937
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

This is a double-blind, randomized, placebo-controlled, Phase 2b/3 two-part adaptive clinical trial. The trial is designed to investigate the pharmacokinetics and the efficacy of multiple dosing regimens of melatonin and to confirm the efficacy and safety of one dosing regimen in prevention for delirium.

Detailed Description

Treatment of the study is a single daily fixed-hour (21h) dose of 15 mL of an oral syrup, at one of the 3 following concentrations of melatonin: 0 mg/ml i.e. 0 mg/day (placebo); 0.02 mg/ml, i.e. 0.3 mg/day (low dose of melatonin) or 0.2 mg/ml, i.e. 3 mg/day (high dose of melatonin). The three dosages will be identical in appearance and volume.Treatment will be administered up to Day-14 (or death or discharge if these occur before Day-14). Randomization will be stratified by center.

Study Timeline

• Study First Submitted: 2018-04-25
• Study First Submitted QC: 2018-05-14
• Study First Posted: 2018-05-15
• Study Start: 2019-02-01
• Primary Completion: 2021-05-01
• Study Completion: 2021-05-20
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-12
• Last Update Posted: 2023-05-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 355

Inclusion Criteria

• Age ≥18 years
• Patient under invasive mechanical ventilation
• Anticipated stay in intensive care unit of at least 48 hours
• Informed consent signed by the patient or a relative or emergency consent

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Exclusion Criteria

• Invasive mechanical ventilation for more than 48 hours
• known pregnancy or breastfeeding
• No understanding of the French language, deafness
• Dementia (Mini Mental State <20) or known chronic psychosis
• Delirium (positive CAM-ICU score) before or at the time of randomization
• Alcohol withdrawal syndrome before or at the time of randomization with Cushman score ≥5
• Inability to use the enteral route, food intolerance with vomiting
• Severe hepatic insufficiency (prothrombin level <30%)
• Ongoing treatment with melatonin or a drug that interacts or modifies its metabolism (fluvoxamine, 5- or 8-methoxypsoralen, estrogen, cimetidine, carbamazepine, rifampicin)
• known allergy to melatonin
• moribund state
• Patient admitted to intensive care for cardiopulmonary arrest, stroke, head trauma, neurosurgery.
• Patient not affiliated to social security
• Patient participating in another interventional clinical study with melatonin and / or for whom delirium is the primary endpoint

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PLACEBO	PLACEBO	Daily administration of identical placebo up to 14 days.
MELATONIN (HIGH DOSE)	MELATONIN (HIGH DOSE)	Daily administration of melatonin by enteral route at 3 mg/day (high dose arm), up to 14 days.
MELATONIN (LOW DOSE)	MELATONIN (LOW DOSE)	Daily administration of melatonin by enteral route at 0.3 mg/day (low dose arm), up to 14 days.

Primary Outcome Measures

Name	Time	Method
Delirium incidence	up to 14 days

Secondary Outcome Measures

Name	Time	Method
Hospital mortality	At day 28	Hospital mortality
ICU mortality	at day 28	ICU mortality
Evaluate number of days alive without coma nor delirium	Up to day 14	days alive without coma nor delirium
Hospital length of stay	at day 28	Hospital length of stay
Duration of delirium	14 days	Duration of delirium
Day 28 Mortality	at day 28	Day 28 Mortality
Duration of mechanical ventilation	Up to day 28	Duration of mechanical ventilation

Trial Locations

Locations (1)

Henri-Mondor Hospital; 🇫🇷 Créteil, Val De Marne, France