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Melatonin to prevent delirium in patients with advanced cancer: a double blind, parallel, randomized, controlled, feasibility trial

BACKGROUND: Delirium is highly problematic in palliative care (PC). Preliminary data indicate a potential role for melatonin to prevent delirium, but no randomized controlled trials (RCTs) are reported in PC. METHODS: Patients aged ≥18 years, with advanced cancer, admitted to an inpatient Palliative...

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Autores principales: Lawlor, Peter G., McNamara-Kilian, Marie T., MacDonald, Alistair R., Momoli, Franco, Tierney, Sallyanne, Lacaze-Masmonteil, Nathalie, Dasgupta, Monidipa, Agar, Meera, Pereira, Jose L., Currow, David C., Bush, Shirley H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579814/
https://www.ncbi.nlm.nih.gov/pubmed/33087111
http://dx.doi.org/10.1186/s12904-020-00669-z
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author Lawlor, Peter G.
McNamara-Kilian, Marie T.
MacDonald, Alistair R.
Momoli, Franco
Tierney, Sallyanne
Lacaze-Masmonteil, Nathalie
Dasgupta, Monidipa
Agar, Meera
Pereira, Jose L.
Currow, David C.
Bush, Shirley H.
author_facet Lawlor, Peter G.
McNamara-Kilian, Marie T.
MacDonald, Alistair R.
Momoli, Franco
Tierney, Sallyanne
Lacaze-Masmonteil, Nathalie
Dasgupta, Monidipa
Agar, Meera
Pereira, Jose L.
Currow, David C.
Bush, Shirley H.
author_sort Lawlor, Peter G.
collection PubMed
description BACKGROUND: Delirium is highly problematic in palliative care (PC). Preliminary data indicate a potential role for melatonin to prevent delirium, but no randomized controlled trials (RCTs) are reported in PC. METHODS: Patients aged ≥18 years, with advanced cancer, admitted to an inpatient Palliative Care Unit (PCU), having a Palliative Performance Scale rating ≥ 30%, and for whom consent was obtained, were included in the study. Patients with delirium on admission were excluded. The main study objectives were to assess the feasibility issues of conducting a double-blind RCT of exogenous melatonin to prevent delirium in PC: recruitment, retention, procedural acceptability, appropriateness of outcome measures, and preliminary efficacy and safety data. Study participants were randomized in a double-blind, parallel designed study to receive daily melatonin 3 mg or placebo orally at 21:00 over 28 days or less if incident delirium, death, discharge or withdrawal occurred earlier. Delirium was diagnosed using the Confusion Assessment Method. Efficacy endpoints in the melatonin and placebo groups were compared using time-to-event analysis: days from study entry to onset of incident delirium. RESULTS: Over 16 months, 60/616 (9.7%; 95% CI: 7.5–12.4%) screened subjects were enrolled. The respective melatonin (n = 30) vs placebo (n = 30) outcomes were: incident delirium in 11/30 (36.7%; 95%CI: 19.9–56.1%) vs 10/30 (33%; 95% CI: 17.3–52.8%); early discharge (6 vs 5); withdrawal (6 vs 3); death (0 vs 1); and 7 (23%) vs 11 (37%) reached the 28-day end point. The 25th percentile time-to-event were 9 and 18 days (log rank, χ(2) = 0.62, p = 0.43) in melatonin and placebo groups, respectively. No serious trial medication-related adverse effects occurred and the core study procedures were acceptable. Compared to those who remained delirium-free during their study participation, those who developed delirium (n = 21) had poorer functional (p = 0.036) and cognitive performance (p = 0.013), and in particular, poorer attentional capacity (p = 0.003) at study entry. CONCLUSIONS: A larger double-blind RCT is feasible, but both subject accrual and withdrawal rates signal a need for multisite collaboration. The apparent trend for shorter time to incident delirium in the melatonin group bodes for careful monitoring in a larger trial. TRIAL REGISTRATION: Registered on July 21st 2014 with ClinicalTrials.gov: NCT02200172.
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spelling pubmed-75798142020-10-22 Melatonin to prevent delirium in patients with advanced cancer: a double blind, parallel, randomized, controlled, feasibility trial Lawlor, Peter G. McNamara-Kilian, Marie T. MacDonald, Alistair R. Momoli, Franco Tierney, Sallyanne Lacaze-Masmonteil, Nathalie Dasgupta, Monidipa Agar, Meera Pereira, Jose L. Currow, David C. Bush, Shirley H. BMC Palliat Care Research Article BACKGROUND: Delirium is highly problematic in palliative care (PC). Preliminary data indicate a potential role for melatonin to prevent delirium, but no randomized controlled trials (RCTs) are reported in PC. METHODS: Patients aged ≥18 years, with advanced cancer, admitted to an inpatient Palliative Care Unit (PCU), having a Palliative Performance Scale rating ≥ 30%, and for whom consent was obtained, were included in the study. Patients with delirium on admission were excluded. The main study objectives were to assess the feasibility issues of conducting a double-blind RCT of exogenous melatonin to prevent delirium in PC: recruitment, retention, procedural acceptability, appropriateness of outcome measures, and preliminary efficacy and safety data. Study participants were randomized in a double-blind, parallel designed study to receive daily melatonin 3 mg or placebo orally at 21:00 over 28 days or less if incident delirium, death, discharge or withdrawal occurred earlier. Delirium was diagnosed using the Confusion Assessment Method. Efficacy endpoints in the melatonin and placebo groups were compared using time-to-event analysis: days from study entry to onset of incident delirium. RESULTS: Over 16 months, 60/616 (9.7%; 95% CI: 7.5–12.4%) screened subjects were enrolled. The respective melatonin (n = 30) vs placebo (n = 30) outcomes were: incident delirium in 11/30 (36.7%; 95%CI: 19.9–56.1%) vs 10/30 (33%; 95% CI: 17.3–52.8%); early discharge (6 vs 5); withdrawal (6 vs 3); death (0 vs 1); and 7 (23%) vs 11 (37%) reached the 28-day end point. The 25th percentile time-to-event were 9 and 18 days (log rank, χ(2) = 0.62, p = 0.43) in melatonin and placebo groups, respectively. No serious trial medication-related adverse effects occurred and the core study procedures were acceptable. Compared to those who remained delirium-free during their study participation, those who developed delirium (n = 21) had poorer functional (p = 0.036) and cognitive performance (p = 0.013), and in particular, poorer attentional capacity (p = 0.003) at study entry. CONCLUSIONS: A larger double-blind RCT is feasible, but both subject accrual and withdrawal rates signal a need for multisite collaboration. The apparent trend for shorter time to incident delirium in the melatonin group bodes for careful monitoring in a larger trial. TRIAL REGISTRATION: Registered on July 21st 2014 with ClinicalTrials.gov: NCT02200172. BioMed Central 2020-10-21 /pmc/articles/PMC7579814/ /pubmed/33087111 http://dx.doi.org/10.1186/s12904-020-00669-z Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Lawlor, Peter G.
McNamara-Kilian, Marie T.
MacDonald, Alistair R.
Momoli, Franco
Tierney, Sallyanne
Lacaze-Masmonteil, Nathalie
Dasgupta, Monidipa
Agar, Meera
Pereira, Jose L.
Currow, David C.
Bush, Shirley H.
Melatonin to prevent delirium in patients with advanced cancer: a double blind, parallel, randomized, controlled, feasibility trial
title Melatonin to prevent delirium in patients with advanced cancer: a double blind, parallel, randomized, controlled, feasibility trial
title_full Melatonin to prevent delirium in patients with advanced cancer: a double blind, parallel, randomized, controlled, feasibility trial
title_fullStr Melatonin to prevent delirium in patients with advanced cancer: a double blind, parallel, randomized, controlled, feasibility trial
title_full_unstemmed Melatonin to prevent delirium in patients with advanced cancer: a double blind, parallel, randomized, controlled, feasibility trial
title_short Melatonin to prevent delirium in patients with advanced cancer: a double blind, parallel, randomized, controlled, feasibility trial
title_sort melatonin to prevent delirium in patients with advanced cancer: a double blind, parallel, randomized, controlled, feasibility trial
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579814/
https://www.ncbi.nlm.nih.gov/pubmed/33087111
http://dx.doi.org/10.1186/s12904-020-00669-z
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