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Mechanically Ventilated PatientsPhase 2/3DEMELNCT03524937

Prevention of Delirium in Intensive Care by Melatonin

A Phase 2/3 study testing MELATONIN (HIGH DOSE) and MELATONIN (LOW DOSE) in people with Mechanically Ventilated Patients, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Mechanically Ventilated Patients
What is being tested?
MELATONIN (HIGH DOSE) and MELATONIN (LOW DOSE)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
355 participants
Where
1 siteFrance
Study dates
1 Feb 2019to 20 May 2021
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 14Show fewer
  • 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 locations and contacts

1 site in 1 country.

France1 site

  • Henri-Mondor Hospital

    Créteil, Val De Marne, 94000

Other trials in France

About this study

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

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.

Read the 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.

Being tested
MELATONIN (HIGH DOSE), MELATONIN (LOW DOSE), PLACEBO
Keywords
Delirium, Mechanical ventilation, Intensive care unit, Prevention, Pharmacokinetics, Melatonin
Medical subject headings
Delirium

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MELATONIN (HIGH DOSE)Drug

    Also called N-acetyl-5-methoxytryptamine

    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)Drug

    Also called N-acetyl-5-methoxytryptamine

    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

  • 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.

Study groups in NCT03524937
Study groupRoleWhat they receive
MELATONIN (LOW DOSE)ExperimentalDaily administration of melatonin by enteral route at 0.3 mg/day (low dose arm), up to 14 days.
Receives: Drug: MELATONIN (LOW DOSE)
MELATONIN (HIGH DOSE)ExperimentalDaily administration of melatonin by enteral route at 3 mg/day (high dose arm), up to 14 days.
Receives: Drug: MELATONIN (HIGH DOSE)
PLACEBOPlacebo comparatorDaily administration of identical placebo up to 14 days.
Receives: Drug: PLACEBO

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Delirium incidence

    Measured: up to 14 days

Secondary outcomes (7)

  1. Day 28 Mortality

    Day 28 Mortality

    Measured: at day 28

  2. Hospital mortality

    Hospital mortality

    Measured: At day 28

  3. ICU mortality

    ICU mortality

    Measured: at day 28

  4. Evaluate number of days alive without coma nor delirium

    days alive without coma nor delirium

    Measured: Up to day 14

  5. Duration of delirium

    Duration of delirium

    Measured: 14 days

  6. Duration of mechanical ventilation

    Duration of mechanical ventilation

    Measured: Up to day 28

  7. Hospital length of stay

    Hospital length of stay

    Measured: at day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 May 2018
  2. Study start1 Feb 2019
  3. Primary completion1 May 2021
  4. Study completion20 May 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
355 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03524937
Sponsor's protocol ID
P160942J
Acronym
DEMEL
Status last verified
May 2023
First submitted
25 Apr 2018
Last updated
15 May 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 15082703

  • 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.

    PubMed 11730446

  • 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.

    PubMed 11430542

  • 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.

    PubMed 17102966

  • 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.

    PubMed 11797025

  • 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.

    PubMed 40608082

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing MELATONIN (HIGH DOSE) and MELATONIN (LOW DOSE) in people with Mechanically Ventilated Patients, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Delirium incidence (time frame: up to 14 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03524937, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2023.

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