{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:11:18Z","timestamp":1791886278402,"version":"4.3.4"},"reference-count":42,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"unspecified","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004351","name":"Sultan Qaboos University","doi-asserted-by":"crossref","award":["RF\/MED\/PHAR\/24\/02"],"award-info":[{"award-number":["RF\/MED\/PHAR\/24\/02"]}],"id":[{"id":"10.13039\/501100004351","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,1,13]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the efficacy of melatonin, a neurohormone regulating the sleep\u2013wake cycle, in preventing delirium within 5\u2009days of hospitalisation among older adult patients (\u226565 years) admitted to general medical wards.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Single-centre, double-blinded, randomised, placebo-controlled trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>General medical wards of a tertiary hospital in Oman.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>Patients aged \u226565 years admitted within 24 hours to general medical wards were screened. Key exclusion criteria included prevalent delirium, use of vasopressors, non-invasive ventilation, intensive or high-dependency unit admission and aphasia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>Participants were randomly assigned to receive either 5\u2009mg or 8\u2009mg of melatonin or a placebo nightly for up to 5\u2009days during hospitalisation or until discharge, whichever occurred first.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Primary and secondary outcome measures<\/jats:title>\n                    <jats:p>The primary outcome was the incidence of delirium within 5\u2009days, assessed using the 3-Minute Diagnostic Confusion Assessment Method. Secondary outcomes included delirium treatment, average sleep duration or sleep maintained, 28-day mortality and 28-day readmission. Analyses followed the intention-to-treat (ITT) principle, with per-protocol (PP) analyses conducted for robustness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The study was terminated early due to futility. At termination, a total of 115 participants were recruited, 109 of whom were included in the ITT analyses: 55 in the melatonin group (5\u2009mg or 8\u2009mg) and 54 in the placebo group. The overall incidence of delirium by day 5 was 2.75%, 3.64% in the melatonin group and 1.85% in the placebo group (p=1.000). No statistically significant differences were found in the average sleep duration (p=0.136), 28-day mortality (3.64% vs 1.85%, p=1.000) or 28-day readmission (21.82% vs 20.37%, p=0.853). PP analyses and subgroup sensitivity yielded similar findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this trial, melatonin did not significantly reduce the incidence of delirium. The lower-than-expected numbers of outcome events and resultant early termination for futility limited the study\u2019s power. As a result, the study findings should be interpreted with caution, and further research is necessary before definitive recommendations can be made.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06509191\">NCT06509191<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-107775","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T13:10:45Z","timestamp":1769519445000},"page":"e107775","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of melatonin versus placebo for the prevention of delirium among medically hospitalised older patients: a double-blinded randomised controlled trial (project RESTORE)"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct06509191","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06509191","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2077-7186","authenticated-orcid":false,"given":"Abdullah M","family":"Al Alawi","sequence":"first","affiliation":[{"name":"Medical Research Center, Sultan Qaboos University, Muscat, Oman"},{"name":"Department of Medicine, Sultan Qaboos University Hospital, University Medical City, Muscat, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8270-6095","authenticated-orcid":false,"given":"Salim","family":"Al Busaidi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Sultan Qaboos University Hospital, University Medical City, Muscat, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Khamis","family":"Al Rasbi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Sultan Qaboos University Hospital, University Medical City, Muscat, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajaa Saleh","family":"Al Farsi","sequence":"additional","affiliation":[{"name":"Ministry of Health, Muscat, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalfan","family":"Al Zeedy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Sultan Qaboos University Hospital, University Medical City, Muscat, Oman"},{"name":"Internal Medicine Residency Training Program, Oman Medical Speciality Board, Al Athaiba, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisha Ramadhan","family":"Al Huraizi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Sultan Qaboos University Hospital, University Medical City, Muscat, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5309-7780","authenticated-orcid":false,"given":"Juhaina Salim","family":"Al-Maqbali","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Science, Sultan Qaboos University, Muscat, Oman"},{"name":"Department of Pharmacy, Sultan Qaboos University Hospital, University Medical City, Muscat, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"2026012705101740000_16.1.e107775.1","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afaa040"},{"key":"2026012705101740000_16.1.e107775.2","doi-asserted-by":"crossref","unstructured":"Davis C , Welch C , McCluskey L . 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