Prevention of Delirium in Intensive Care by Melatonin

Mechanically Ventilated Patients Clinical Trial

— DEMEL  

Official title:

Prevention of Delirium in Intensive Care by Melatonin: a Prospective, Multicentre, Randomized, Double Blind, Placebo, Multi-arm, Multi-stage Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03524937
• Other study ID #: P160942J
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: February 1, 2019
• Est. completion date: May 20, 2021

Study information

• Verified date: May 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 355
• Est. completion date: May 20, 2021
• Est. primary completion date: May 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Delirium
• Mechanically Ventilated Patients

Intervention

Drug:
• MELATONIN (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
• MELATONIN (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
• PLACEBO
Study drug will be given at 21:00h daily, starting on the day of enrolment until ICU discharge, death, or up to 14 days.

Locations

Country	Name	City	State
France	Henri-Mondor Hospital	Créteil	Val De Marne

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (5)

Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y. Intensive Care Delirium Screening Checklist: evaluation of a new screening tool. Intensive Care Med. 2001 May;27(5):859-64. doi: 10.1007/s001340100909. — View Citation

Ely EW, Gautam S, Margolin R, Francis J, May L, Speroff T, Truman B, Dittus R, Bernard R, Inouye SK. The impact of delirium in the intensive care unit on hospital length of stay. Intensive Care Med. 2001 Dec;27(12):1892-900. doi: 10.1007/s00134-001-1132-2. Epub 2001 Nov 8. — View Citation

Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R, Hart RP, Dittus R. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA. 2001 Dec 5;286(21):2703-10. doi: 10.1001/jama.286.21.2703. — View Citation

Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14;291(14):1753-62. doi: 10.1001/jama.291.14.1753. — View Citation

Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors and consequences of ICU delirium. Intensive Care Med. 2007 Jan;33(1):66-73. doi: 10.1007/s00134-006-0399-8. Epub 2006 Nov 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Delirium incidence		up to 14 days
Secondary	Day 28 Mortality	Day 28 Mortality	at day 28
Secondary	Hospital mortality	Hospital mortality	At day 28
Secondary	ICU mortality	ICU mortality	at day 28
Secondary	Evaluate number of days alive without coma nor delirium	days alive without coma nor delirium	Up to day 14
Secondary	Duration of delirium	Duration of delirium	14 days
Secondary	Duration of mechanical ventilation	Duration of mechanical ventilation	Up to day 28
Secondary	Hospital length of stay	Hospital length of stay	at day 28