Melatonin for Prevention of Delirium in Critically Ill Patients (MELLOW-1)

Mount Sinai Hospital, Canada

Status and phase: Unknown; Phase 2

Conditions: Delirium

Treatments: Drug: Melatonin; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02615340

4000145150

Details and patient eligibility

About

The purpose of this study is to determine the feasibility of conducting a randomized controlled trial (RCT) with melatonin for prevention of delirium in critically ill adult patients. 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.

Full description

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.

Enrollment: 69 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Critically ill patients ≥18 years of age
2. Anticipated ICU stay of >48 hours
3. 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)
4. Consent to participate.

Exclusion criteria

1. ICU admission of >48 hours prior to screening
2. 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)
3. Screened delirium positive prior to randomization (ICDSC score ≥4 out of 8)
4. Anticipated withdrawal in next 48 hours
5. 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
6. Unable to communicate in English or French (Montreal site)
7. 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)
8. Active seizures
9. Known pregnancy
10. Legal blindness
11. Known allergy to melatonin

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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69 participants in 3 patient groups, including a placebo group

Enteral melatonin 0.5 mg

Active Comparator group

Description:

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)

Treatment:

Drug: Melatonin

Enteral melatonin 2 mg

Active Comparator group

Description:

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)

Treatment:

Drug: Melatonin

Enteral matched placebo

Placebo Comparator group

Description:

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)

Treatment:

Drug: Placebo