Prevention of Delirium in Intensive Care by Melatonin: a Prospective, Multicentre, Randomized, Double Blind, Placebo, Multi-arm, Multi-stage Study
Overview
- Phase
- Phase 2
- Intervention
- PLACEBO
- Conditions
- Mechanically Ventilated Patients
- Sponsor
- Assistance Publique - Hôpitaux de Paris
- Enrollment
- 355
- Locations
- 1
- Primary Endpoint
- Delirium incidence
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
PLACEBO
Daily administration of identical placebo up to 14 days.
Intervention: PLACEBO
MELATONIN (LOW DOSE)
Daily administration of melatonin by enteral route at 0.3 mg/day (low dose arm), up to 14 days.
Intervention: MELATONIN (LOW DOSE)
MELATONIN (HIGH DOSE)
Daily administration of melatonin by enteral route at 3 mg/day (high dose arm), up to 14 days.
Intervention: MELATONIN (HIGH DOSE)
Outcomes
Primary Outcomes
Delirium incidence
Time Frame: up to 14 days
Secondary Outcomes
- Hospital length of stay(at day 28)
- Duration of delirium(14 days)
- Day 28 Mortality(at day 28)
- Hospital mortality(At day 28)
- ICU mortality(at day 28)
- Evaluate number of days alive without coma nor delirium(Up to day 14)
- Duration of mechanical ventilation(Up to day 28)