Mechanically Ventilated Patients
Conditions
Keywords
Delirium, Mechanical ventilation, Intensive care unit, Prevention, Pharmacokinetics, Melatonin
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.
Interventions
DRUGMELATONIN (HIGH DOSE)
Enteral melatonin (3mg) will be given at 21:00h daily, starting on the day of enrolment until ICU discharge, death, or up to 14 days
DRUGMELATONIN (LOW DOSE)
Enteral melatonin (0.3mg ) will be given at 21:00h daily, starting on the day of enrolment until ICU discharge, death, or up to 14 days
DRUGPLACEBO
Study drug will be given at 21:00h daily, starting on the day of enrolment until ICU discharge, death, or up to 14 days.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Delirium incidence | up to 14 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Day 28 Mortality | at day 28 | Day 28 Mortality |
| Duration of mechanical ventilation | Up to day 28 | Duration of mechanical ventilation |
| Hospital length of stay | at day 28 | Hospital length of stay |
| Duration of delirium | 14 days | Duration of delirium |
Countries
France
Outcome results
None listed