Melatonin for Treatment of Delirium in Critically Ill Adult Patients

Официальное название

DELIRE-ICU: A Randomised Controlled Feasibility Trial of Melatonin vs Placebo in the Treatment of Delirium in the Intensive Care Unit

Обзор

The purpose of this study is to determine the feasibility of conducting a randomized controlled trial (RCT) with melatonin for treatment of delirium in critically ill adult patients. From a feasibility perspective, the investigators believe that the proposed design will achieve the minimum enrollment rate necessary to conduct a future RCT on a larger scale.

Подробное описание

The prevalence of delirium is high in the intensive care unit (ICU), yet there is no pharmacological treatment that has been proven effective. The investigators hypothesize that melatonin, given on a daily basis at 21:00, will safely decrease the mean duration of a delirium episode in ICU patients. The current literature evaluating melatonin as a treatment for delirium is lacking, therefore more studies are needed.

It is estimated that an alteration of sleep pattern can be found in up to 75% of patients with delirium. This raises the hypothesis that prevention and treatment of sleep disorders could potentially improve delirium. Sleep and circadian rhythm disturbances are associated with low endogenous melatonin secretion and studies have shown that it also occurs in patients with delirium.

Thus, the objective is to conduct a phase II double blind, placebo-controlled randomized trial comparing melatonin 9 mg to placebo to evaluate the feasibility of a future large-scale RCT. Participants will be followed during their stay in the ICU and after their transfer on another unit up to a maximum of 14 days. Feasibility of the larger trial will mainly be based on enrollment rates.

Вмешательства

• Препарат Melatonin
  Study drug will be given at 21:00 daily, starting on the day of enrolment until delirium resolution, hospital discharge, death, or up to 14 days. The study medication will be given by mouth (PO or per os) or, if needed, via the feeding tube.
• Препарат Placebo
  Study drug will be given at 21:00 daily, starting on the day of enrolment until delirium resolution, hospital discharge, death, or up to 14 days. The study medication will be given by mouth (PO or per os) or, if needed, via the feeding tube.

Первичные конечные точки

• Feasibility: Enrollment rate [Срок оценки: 8 months]
• Clinical: Duration of delirium [Срок оценки: 14 days]

Вторичные конечные точки (3)

• Feasibility: Study adherence [Срок оценки: 8 months]
• Feasibility: Consent rate [Срок оценки: 8 months]
• Clinical: Adverse events [Срок оценки: 14 days]

Критерии участия

Критерии включения

• Patients aged 18 years or older admitted to the intensive care unit;
• Anticipated ICU stay > 48 hours;
• ICDSC score greater than or equal to 4 for a maximum of 48 hours prior to randomization.

Критерии исключения

• Known allergy or hypersensitivity to melatonin or to ingredients in ORA-BLEND SF®;
• Use of melatonin within 24 hours prior to randomization;
• Presence of severe structural brain injury (intracranial hemorrhage or traumatic brain injury), severe major neurocognitive disorder, advanced neurodegenerative disease or hepatic encephalopathy;
• Diagnosis of schizophrenia, bipolar affective disorder, psychotic depression, uremic encephalopathy or alcohol withdrawal;
• Presence of active seizures, coma, aphasia or severe intellectual disability;
• Limited short-term vital prognosis;
• Diagnosis of delirium prior to ICU admission;
• Pregnancy or breastfeeding;
• Absolute contraindication to receive enteral medication;
• Inability to understand or speak English or French;
• Total blindness.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• Hopital Maisonneuve-Rosemont — Montreal

Публикации

• Flacker JM, Lipsitz LA. Neural mechanisms of delirium: current hypotheses and evolving concepts. J Gerontol A Biol Sci Med Sci. 1999 Jun;54(6):B239-46. doi: 10.1093/gerona/54.6.b239. PMID 10411009
• Pandharipande PP, Morandi A, Adams JR, Girard TD, Thompson JL, Shintani AK, Ely EW. Plasma tryptophan and tyrosine levels are independent risk factors for delirium in critically ill patients. Intensive Care Med. 2009 Nov;35(11):1886-92. doi: 10.1007/s00134-009-1573-6. Epub 2009 Jul 9. PMID 19588122
• Stollings JL, Kotfis K, Chanques G, Pun BT, Pandharipande PP, Ely EW. Delirium in critical illness: clinical manifestations, outcomes, and management. Intensive Care Med. 2021 Oct;47(10):1089-1103. doi: 10.1007/s00134-021-06503-1. Epub 2021 Aug 16. PMID 34401939
• Sun T, Sun Y, Huang X, Liu J, Yang J, Zhang K, Kong G, Han F, Hao D, Wang X. Sleep and circadian rhythm disturbances in intensive care unit (ICU)-acquired delirium: a case-control study. J Int Med Res. 2021 Mar;49(3):300060521990502. doi: 10.1177/0300060521990502. PMID 33730927
• Weinhouse GL, Schwab RJ, Watson PL, Patil N, Vaccaro B, Pandharipande P, Ely EW. Bench-to-bedside review: delirium in ICU patients - importance of sleep deprivation. Crit Care. 2009;13(6):234. doi: 10.1186/cc8131. Epub 2009 Dec 7. PMID 20053301
• Farasat S, Dorsch JJ, Pearce AK, Moore AA, Martin JL, Malhotra A, Kamdar BB. Sleep and Delirium in Older Adults. Curr Sleep Med Rep. 2020;6(3):136-148. doi: 10.1007/s40675-020-00174-y. Epub 2020 Jul 27. PMID 32837850
• Burry L, Scales D, Williamson D, Foster J, Mehta S, Guenette M, Fan E, Detsky M, Azad A, Bernard F, Rose L. Feasibility of melatonin for prevention of delirium in critically ill patients: a protocol for a multicentre, randomised, placebo-controlled study. BMJ Open. 2017 Mar 30;7(3):e015420. doi: 10.1136/bmjopen-2016-015420. PMID 28363933
• Thabane L, Ma J, Chu R, Cheng J, Ismaila A, Rios LP, Robson R, Thabane M, Giangregorio L, Goldsmith CH. A tutorial on pilot studies: the what, why and how. BMC Med Res Methodol. 2010 Jan 6;10:1. doi: 10.1186/1471-2288-10-1. PMID 20053272

Идентификаторы

NCT: NCT05713877 · 2023-3247

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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