NCT03524937

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
355

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Feb 2019

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 25, 2018

Completed
20 days until next milestone

First Posted

Study publicly available on registry

May 15, 2018

Completed
9 months until next milestone

Study Start

First participant enrolled

February 1, 2019

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2021

Completed
19 days until next milestone

Study Completion

Last participant's last visit for all outcomes

May 20, 2021

Completed
Last Updated

May 15, 2023

Status Verified

May 1, 2023

Enrollment Period

2.2 years

First QC Date

April 25, 2018

Last Update Submit

May 12, 2023

Conditions

Mechanically Ventilated Patients

Keywords

DeliriumMechanical ventilationIntensive care unitPreventionPharmacokineticsMelatonin

Outcome Measures

Primary Outcomes (1)

  • Delirium incidence

    up to 14 days

Secondary Outcomes (7)

  • 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 delirium

    14 days

  • +2 more secondary outcomes

Study Arms (3)

MELATONIN (LOW DOSE)

EXPERIMENTAL

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

Drug: MELATONIN (LOW DOSE)

MELATONIN (HIGH DOSE)

EXPERIMENTAL

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

Drug: MELATONIN (HIGH DOSE)

PLACEBO

PLACEBO COMPARATOR

Daily administration of identical placebo up to 14 days.

Drug: PLACEBO

Interventions

MELATONIN (HIGH DOSE)DRUG

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

Also known as: N-acetyl-5-methoxytryptamine
MELATONIN (HIGH DOSE)
MELATONIN (LOW DOSE)DRUG

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

Also known as: N-acetyl-5-methoxytryptamine
MELATONIN (LOW DOSE)
PLACEBODRUG

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

PLACEBO

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Henri-Mondor Hospital

Créteil, Val De Marne, 94000, France

Location

Related Publications (6)

  • 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.

    PMID: 15082703BACKGROUND

  • 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.

    PMID: 11730446BACKGROUND

  • 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.

    PMID: 11430542BACKGROUND

  • 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.

    PMID: 17102966BACKGROUND

  • 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.

    PMID: 11797025BACKGROUND

  • Mekontso Dessap A, Ricard JD, Contou D, Desnos C, Decavele M, Sonneville R, Vivier E, Terzi N, Callahan JC, Jochmans S, Leon R, Carreira S, Nseir S, Chemouni F, Castelain V, Paul M, Benoist JF, Audureau E, Razazi K; CARMAS and the REVA research networks, on behalf of the DEMEL Investigators. Melatonin for prevention of delirium in patients receiving mechanical ventilation in the intensive care unit: a multiarm multistage adaptive randomized controlled clinical trial (DEMEL). Intensive Care Med. 2025 Jul;51(7):1292-1305. doi: 10.1007/s00134-025-08002-z. Epub 2025 Jul 3.

    PMID: 40608082DERIVED

MeSH Terms

Conditions

Delirium

Interventions

Melatonin

Condition Hierarchy (Ancestors)

ConfusionNeurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and SymptomsNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

TryptaminesIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsHormonesHormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

  • France GUYOT

    DRCI-Assistance Publique des Hopitaux de paris

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 25, 2018

First Posted

May 15, 2018

Study Start

February 1, 2019

Primary Completion

May 1, 2021

Study Completion

May 20, 2021

Last Updated

May 15, 2023

Record last verified: 2023-05

Data Sharing

IPD Sharing
Will not share

Locations

FR(1)