Prevention of Delirium in Intensive Care by Melatonin (DEMEL)

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 3; Phase 2

Conditions: Mechanically Ventilated Patients

Treatments: Drug: MELATONIN (LOW DOSE); Drug: PLACEBO; Drug: MELATONIN (HIGH DOSE)

Study type: Interventional

Funder types: Other

Identifiers

NCT03524937

P160942J

Details and patient eligibility

About

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.

Full 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.

Enrollment: 355 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

355 participants in 3 patient groups, including a placebo group

MELATONIN (LOW DOSE)

Experimental group

Description:

Daily administration of melatonin by enteral route at 0.3 mg/day (low dose arm), up to 14 days.

Treatment:

Drug: MELATONIN (LOW DOSE)

MELATONIN (HIGH DOSE)

Experimental group

Description:

Daily administration of melatonin by enteral route at 3 mg/day (high dose arm), up to 14 days.

Treatment:

Drug: MELATONIN (HIGH DOSE)

PLACEBO

Placebo Comparator group

Description:

Daily administration of identical placebo up to 14 days.

Treatment:

Drug: PLACEBO