- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT02615340
Melatonin for Prevention of Delirium in Critically Ill Patients (MELLOW-1)
Feasibility of Melatonin for Prevention of Delirium in Critically Ill Patients: a Multi-centre, Randomized, Placebo-controlled Study.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
The available evidence indicates melatonin may decrease the incidence of delirium in non-critically ill patient populations; however, trials in the critically ill are lacking. The investigators hypothesize that melatonin, administered on a scheduled nightly basis during ICU admission, will be efficacious and safe for the prevention of delirium in critically ill adults. The null hypothesis is that there is no difference in delirium incidence between placebo and melatonin. Prior to conducting an adequately powered multi-centre, blinded randomized, placebo-controlled trial in critically ill patients, there is a need for a better understanding of melatonin pharmacokinetics (PK) in critically ill patients. This will help to determine appropriate dosing, drug administration issues (specifically protocol adherence), adverse drug effects, and recruitment rates based on inclusion and exclusion criteria.
The specific aim is to conduct a phase II triple blind, placebo-controlled randomized trial comparing two doses of melatonin (low dose = 0.5 mg and high dose = 2.0 mg) to assess the feasibility of a future full-scale RCT. Feasibility of the larger trial will be based on protocol adherence and participant recruitment rates. Data on PK properties of melatonin will be assessed to determine dosing for future studies of melatonin for delirium prevention in the critically ill.
Type d'étude
Inscription (Anticipé)
Phase
- Phase 2
Contacts et emplacements
Coordonnées de l'étude
- Nom: Lisa Burry, PharmD
- Numéro de téléphone: 4820 4165864800
- E-mail: lisa.burry@sinaihealthsystem.ca
Sauvegarde des contacts de l'étude
- Nom: Louise Rose
- Numéro de téléphone: 416978-3492
- E-mail: louise.rose@utoronto.ca
Lieux d'étude
-
-
Ontario
-
Toronto, Ontario, Canada, M5G1X5
- Recrutement
- Mount Sinai Hospital
-
Contact:
- Lisa Burry, PharmD
- E-mail: lisa.burry@sinaihealthsystem.ca
-
Chercheur principal:
- Lisa Burry
-
Toronto, Ontario, Canada
- Recrutement
- Sunnybrook Health Sciences Centre
-
Contact:
- Damon Scales
- E-mail: damon.scales@sunnybrook.ca
-
Chercheur principal:
- Damon Scales, MD PhD
-
Chercheur principal:
- Louise Rose, PhD
-
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Quebec
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Montréal, Quebec, Canada
- Pas encore de recrutement
- Hopital du Sacre-Coeur
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Contact:
- David Williamson
- E-mail: david.williamson@umontreal.ca
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Chercheur principal:
- David Williamson, PhD
-
Chercheur principal:
- Francis Bernard, MD
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Critically ill patients ≥18 years of age
- Anticipated ICU stay of >48 hours
- Able to receive enteral administration of study drug (i.e. by mouth or any feeding tube = naso- or oro- or percutaneous gastric or post-pyloric feeding tube)
- Consent to participate.
Exclusion Criteria:
- ICU admission of >48 hours prior to screening
- Unable to assess for delirium (e.g. comatose defined as SAS 1 or 2 or either 'No Response' Score A or B on ICDSC, chemically paralyzed with neuromuscular blocking drugs)
- Screened delirium positive prior to randomization (ICDSC score ≥4 out of 8)
- Anticipated withdrawal in next 48 hours
- Known history of severe cognitive or neurodegenerative disease (e.g. dementia, Parkinson's disease) or severe structural brain injury (e.g. traumatic brain injury, intracranial hemorrhage) as the ICDSC assessment tool has not been validated in these patient populations
- Unable to communicate in English or French (Montreal site)
- Contraindications to receiving any enteral medication (defined as absolute contraindication to enteral nutrition such as gastrointestinal obstruction, perforation, recent upper GI surgery, no enteral access)
- Active seizures
- Known pregnancy
- Legal blindness
- Known allergy to melatonin
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: La prévention
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Quadruple
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
---|---|
Comparateur actif: Enteral melatonin 0.5 mg
Melatonin 0.5 mg from the 1mg/mL oral suspension qs to 5 mL with Oral Mix SF (sugar-free flavoured suspending vehicle) (final concentration of 0.1 mg/mL; final volume in the oral syringe will be 5 mL)
|
Study drug will be given at 21:00 - 23:59 daily, starting on the day of enrolment until ICU discharge, death, or up to 14 days, as most critically ill patients are at greatest risk of delirium in the first two weeks of admission.
The study medication will be given by mouth (PO or per os) or if needed, via the feeding tube followed by a flush with 20mL water.
Doses can be given up to midnight if administration needs to be delayed for procedures or investigations.
Autres noms:
|
Comparateur actif: Enteral melatonin 2 mg
Melatonin 2 mg from the 1mg/mL oral suspension qs to 5 mL with Oral Mix SF (sugar-free flavoured suspending vehicle) (final concentration 0.4 mg/mL; final volume in the oral syringe will be 5 mL)
|
Study drug will be given at 21:00 - 23:59 daily, starting on the day of enrolment until ICU discharge, death, or up to 14 days, as most critically ill patients are at greatest risk of delirium in the first two weeks of admission.
The study medication will be given by mouth (PO or per os) or if needed, via the feeding tube followed by a flush with 20mL water.
Doses can be given up to midnight if administration needs to be delayed for procedures or investigations.
Autres noms:
|
Comparateur placebo: Enteral matched placebo
Melatonin 0 mg qs to 5 mL with Oral Mix SF (sugar-free flavoured suspending vehicle) (final concentration 0 mg/mL; final volume in the oral syringe will be 5 mL)
|
Study drug will be given at 21:00 - 23:59 daily, starting on the day of enrolment until ICU discharge, death, or up to 14 days, as most critically ill patients are at greatest risk of delirium in the first two weeks of admission.
The study medication will be given by mouth (PO or per os) or if needed, via the feeding tube followed by a flush with 20mL water.
Doses can be given up to midnight if administration needs to be delayed for procedures or investigations.
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Feasibility: Study adherence
Délai: 1 year
|
Investigators will calculate protocol adherence as the overall proportion of administered doses in the prescribed dose administration window (between 21:00 and to 23:59 hours) divided by total number of eligible study days.
|
1 year
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Feasibility: Trial recruitment
Délai: 1 year
|
Proportion of ICU patients screened that meet study inclusion criteria, the number of patients excluded and reasons for exclusion, and the consent rate of eligible participants.
|
1 year
|
Feasibility: Time in motion (minutes)
Délai: 1 year
|
Research coordinators at each site will capture the amount of time (minutes) taken to screen, consent, and enrol patients, complete study procedures, and collect data.
|
1 year
|
Pharmacokinetic: Peak melatonin concentration (Cmax)
Délai: 24 hours
|
Peak melatonin concentration. Plasma melatonin concentrations measured by mass spectrometry. N=5 from each study arm of Mount Sinai Hospital site. On study day 1, eight blood samples (4 mL each) will be collected at the following intervals, from the time of first study drug dose to the following morning (time 0, 0.5, 1, 2, 4, 6, 8, 12 hours). |
24 hours
|
Pharmacokinetic: Time of peak melatonin concentration (Tmax)
Délai: 24 hours
|
Time of peak melatonin concentration (Tmax). Plasma melatonin concentrations measured by mass spectrometry. N=5 from each study arm of Mount Sinai Hospital site. On study day 1, eight blood samples (4 mL each) will be collected at the following intervals, from the time of first study drug dose to the following morning (time 0, 0.5, 1, 2, 4, 6, 8, 12 hours). |
24 hours
|
Pharmacokinetic: Morning melatonin concentration (C9AM)
Délai: 24 hours
|
Morning melatonin concentration (C9AM). Plasma melatonin concentrations measured by mass spectrometry. N=5 from each study arm of Mount Sinai Hospital site. On study day 1, eight blood samples (4 mL each) will be collected at the following intervals, from the time of first study drug dose to the following morning (time 0, 0.5, 1, 2, 4, 6, 8, 12 hours). |
24 hours
|
Pharmacokinetic: Melatonin half-life (T½)
Délai: 24 hours
|
Melatonin half-life (T½). Plasma melatonin concentrations measured by mass spectrometry. N=5 from each study arm of Mount Sinai Hospital site. On study day 1, eight blood samples (4 mL each) will be collected at the following intervals, from the time of first study drug dose to the following morning (time 0, 0.5, 1, 2, 4, 6, 8, 12 hours). |
24 hours
|
Pharmacokinetic: Mean apparent clearance (CL/F)
Délai: 24 hours
|
Mean apparent clearance (CL/F). Plasma melatonin concentrations measured by mass spectrometry. N=5 from each study arm of Mount Sinai Hospital site. On study day 1, eight blood samples (4 mL each) will be collected at the following intervals, from the time of first study drug dose to the following morning (time 0, 0.5, 1, 2, 4, 6, 8, 12 hours). |
24 hours
|
Pharmacokinetic: Mean apparent volume distribution (V/F)
Délai: 24 hours
|
Mean apparent volume distribution (V/F). Plasma melatonin concentrations measured by mass spectrometry. N=5 from each study arm of Mount Sinai Hospital site. On study day 1, eight blood samples (4 mL each) will be collected at the following intervals, from the time of first study drug dose to the following morning (time 0, 0.5, 1, 2, 4, 6, 8, 12 hours). |
24 hours
|
Pharmacokinetic: Area under the concentration-time curve (AUC)
Délai: 24 hours
|
Area under the concentration-time curve (AUC). Plasma melatonin concentrations measured by mass spectrometry. N=5 from each study arm of Mount Sinai Hospital site. On study day 1, eight blood samples (4 mL each) will be collected at the following intervals, from the time of first study drug dose to the following morning (time 0, 0.5, 1, 2, 4, 6, 8, 12 hours). |
24 hours
|
Clinical: Adverse events
Délai: 14 days
|
Adverse events reported by the participant, family, or treating team.
The following potential adverse effects will be collected: morning drowsiness (Sedation Agitation Scale (SAS) score <3 or patient's self report of drowsiness between 07:00h and 12:00h), headache, and vivid dreams.
|
14 days
|
Clinical: Delirium incidence
Délai: 14 days
|
Intensive Care Delirium Screening Checklist (ICDSC) administered daily.
Delirium defined as an ICDSC score ≥4.
|
14 days
|
Clinical: Delirium time to onset and duration (days)
Délai: 14 days
|
Time to onset of first ICDSC score ≥4, and number of days with ICDSC score ≥4.
|
14 days
|
Clinical: Sleep
Délai: 14 days
|
Richards Campbell Sleep Questionnaire (RCSQ) administered daily, where possible.
Patients with or without the assistance of their nurse will be asked to complete the questions of the RCSQ each morning.
Nurses will not complete the RCSQ if the patient is unable to verbalize, as poor correlation has been shown between patient and nursing scores.
|
14 days
|
Clinical: Duration of mechanical ventilation
Délai: ICU admission
|
Duration of mechanical ventilation (days)
|
ICU admission
|
Clinical: ICU length of stay
Délai: ICU admission
|
Duration of stay for index ICU admission (days)
|
ICU admission
|
Clinical: Hospital length of stay
Délai: 1 year
|
Duration of stay for admission involving trial enrolment (days)
|
1 year
|
Clinical: ICU mortality
Délai: 1 year
|
Number of deaths during index ICU admission
|
1 year
|
Clinical: Hospital mortality
Délai: 1 year
|
Number of deaths during hospital admission
|
1 year
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Lisa Burry, PharmD, Mount Sinai Hospital
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Anticipé)
Achèvement de l'étude (Anticipé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Les troubles mentaux
- Maladies du système nerveux
- Manifestations neurologiques
- Confusion
- Manifestations neurocomportementales
- Troubles neurocognitifs
- Délire
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Dépresseurs du système nerveux central
- Agents protecteurs
- Antioxydants
- Mélatonine
Autres numéros d'identification d'étude
- 4000145150
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
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