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Prevention of Delirium in Intensive Care by Melatonin (DEMEL)

Primary Purpose

Mechanically Ventilated Patients

Status

Completed

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

MELATONIN (HIGH DOSE)

MELATONIN (LOW DOSE)

PLACEBO

About this trial

This is an interventional treatment trial for Mechanically Ventilated Patients focused on measuring Delirium, Mechanical ventilation, Intensive care unit, Prevention, Pharmacokinetics, Melatonin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Henri-Mondor Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

MELATONIN (LOW DOSE)

MELATONIN (HIGH DOSE)

PLACEBO

Arm Description

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

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

Daily administration of identical placebo up to 14 days.

Outcomes

Primary Outcome Measures

Delirium incidence

Secondary Outcome Measures

Day 28 Mortality

Hospital mortality

ICU mortality

Evaluate number of days alive without coma nor delirium

days alive without coma nor delirium

Duration of delirium

Duration of mechanical ventilation

Hospital length of stay

Full Information

NCT ID

NCT03524937

First Posted

April 25, 2018

Last Updated

May 12, 2023

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT03524937

Brief Title

Prevention of Delirium in Intensive Care by Melatonin

Acronym

DEMEL

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Completed

Study Start Date

February 1, 2019 (Actual)

Primary Completion Date

May 1, 2021 (Actual)

Study Completion Date

May 20, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Mechanically Ventilated Patients

Keywords

Delirium, Mechanical ventilation, Intensive care unit, Prevention, Pharmacokinetics, Melatonin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

355 (Actual)

8. Arms, Groups, and Interventions

Arm Title

MELATONIN (LOW DOSE)

Arm Type

Experimental

Arm Description

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

Arm Title

MELATONIN (HIGH DOSE)

Arm Type

Experimental

Arm Description

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

Arm Title

PLACEBO

Arm Type

Placebo Comparator

Arm Description

Daily administration of identical placebo up to 14 days.

Intervention Type

Drug

Intervention Name(s)

MELATONIN (HIGH DOSE)

Other Intervention Name(s)

N-acetyl-5-methoxytryptamine

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

MELATONIN (LOW DOSE)

Other Intervention Name(s)

N-acetyl-5-methoxytryptamine

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

PLACEBO

Intervention Description

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

Primary Outcome Measure Information:

Title

Delirium incidence

Time Frame

up to 14 days

Secondary Outcome Measure Information:

Title

Day 28 Mortality

Description

Day 28 Mortality

Time Frame

at day 28

Title

Hospital mortality

Description

Hospital mortality

Time Frame

At day 28

Title

ICU mortality

Description

ICU mortality

Time Frame

at day 28

Title

Evaluate number of days alive without coma nor delirium

Description

days alive without coma nor delirium

Time Frame

Up to day 14

Title

Duration of delirium

Description

Duration of delirium

Time Frame

14 days

Title

Duration of mechanical ventilation

Description

Duration of mechanical ventilation

Time Frame

Up to day 28

Title

Hospital length of stay

Description

Hospital length of stay

Time Frame

at day 28

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

France GUYOT

Organizational Affiliation

DRCI-Assistance Publique des Hopitaux de paris

Official's Role

Study Chair

Facility Information:

Facility Name

Henri-Mondor Hospital

City

Créteil

State/Province

Val De Marne

ZIP/Postal Code

94000

Country

France

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

15082703

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.

Results Reference

background

PubMed Identifier

11730446

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.

Results Reference

background

PubMed Identifier

11430542

Citation

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.

Results Reference

background

PubMed Identifier

17102966

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.

Results Reference

background

PubMed Identifier

11797025

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.

Results Reference

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Prevention of Delirium in Intensive Care by Melatonin

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