Study protocol for a prospective randomised double-blind placebo-controlled clinical trial investigating a Better Outcome with Melatonin compared to Placebo Administered to normalize sleep–wake cycle and treat hypoactive ICU Delirium: the Basel BOMP-AID study

Abstract

IntroductionDelirium is frequently observed in the intensive care unit (ICU) population, in particular. Until today, there is no evidence for any reliable pharmacological intervention to treat delirium. The Basel BOMP-AID (BetterOutcome withMelatonin compared toPlaceboAdministered to normalize sleep-wake cycle and treat hypoactiveICUDelirium) randomised trial targets improvement of hypoactive delirium therapy in critically ill patients and will be conducted as a counterpart to the Basel ProDex Study (Study Protocol, BMJ Open, July 2017) on hyperactive and mixed delirium. The aim of the BOMP-AID trial is to assess the superiority of melatonin to placebo for the treatment of hypoactive delirium in the ICU. The study hypothesis is based on the assumption that melatonin administered at night restores a normal circadian rhythm, and that restoration of a normal circadian rhythm will cure delirium.Methods and analysisThe Basel BOMP-AID study is an investigator-initiated, single-centre, randomised controlled clinical trial for the treatment of hypoactive delirium with the once daily oral administration of melatonin 4 mg versus placebo in 190 critically ill patients. The primary outcome measure is delirium duration in 8-hour shifts. Secondary outcome measures include delirium-free days and death at 28 days after study inclusion, number of ventilator days, length of ICU and hospital stay, and sleep quality. Patients will be followed after 3 and 12 months for activities of daily living and mortality assessment. Sample size was calculated to demonstrate superiority of melatonin compared with placebo regarding the duration of delirium. Results will be presented using an intention-to-treat approach.Ethics and disseminationThis study has been approved by the Ethics Committee of Northwestern and Central Switzerland and will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the International Conference on Harmonisation (ICH) of technical requirements for registration of pharmaceuticals for human use; Good Clinical Practice (GCP) or ISO EN 14155 (as far as applicable), as well as all national legal and regulatory requirements. Study results will be presented in international conferences and published in a peer-reviewed journal.Trial registration numberNCT03438526.Protocol versionClinical Study Protocol Version 3, 10.03.2019.

Effect of Perioperative Dexmedetomidine Infusion on Postoperative Delirium in Elderly Patients Undergoing Oral and Maxillofacial Surgery: A Randomized Controlled Clinical Trial

“…The reason may be that dexmedetomidine improves sleep quality but does not alter sleep cycles, and normalizing sleep cycles was more effective in reducing delirium. 36 In this study, we found that dexmedetomidine did not increase the incidence of adverse events, which was consistent with a previously published review, 37 but monitoring and management still should be taken to ensure clinical safety.…”

“…The reason may be that dexmedetomidine improves sleep quality but does not alter sleep cycles, and normalizing sleep cycles was more effective in reducing delirium. 36 …”