Feasibility of Melatonin for Prevention of Delirium in Critically Ill Patients: a Multi-centre, Randomized, Placebo-controlled Study.
试验速览
- 阶段
- 2 期
- 入组人数
- 69
- 试验地点
- 3
- 主要终点
- Feasibility: Study adherence
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
All study personnel, patients, and their families will remain blinded. Treatment allocation will only be known to the clinical trials pharmacist, who will perform subject randomization.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
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)
干预措施: Melatonin (Drug)
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)
干预措施: Melatonin (Drug)
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)
干预措施: Placebo (Drug)
结局指标
主要结局
Feasibility: Study adherence
时间窗: 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.
次要结局
- Clinical: ICU mortality(1 year)
- Clinical: Hospital mortality(1 year)
- Feasibility: Trial recruitment(1 year)
- Pharmacokinetic: Peak melatonin concentration (Cmax)(24 hours)
- Pharmacokinetic: Time of peak melatonin concentration (Tmax)(24 hours)
- Pharmacokinetic: Morning melatonin concentration (C9AM)(24 hours)
- Pharmacokinetic: Melatonin half-life (T½)(24 hours)
- Pharmacokinetic: Mean apparent clearance (CL/F)(24 hours)
- Pharmacokinetic: Mean apparent volume distribution (V/F)(24 hours)
- Feasibility: Time in motion (minutes)(1 year)
- Clinical: Delirium incidence(14 days)
- Clinical: Delirium time to onset and duration (days)(14 days)
- Clinical: Sleep(14 days)
- Pharmacokinetic: Area under the concentration-time curve (AUC)(24 hours)
- Clinical: Adverse events(14 days)
- Clinical: Duration of mechanical ventilation(ICU admission)
- Clinical: ICU length of stay(ICU admission)
- Clinical: Hospital length of stay(1 year)