{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T13:22:28Z","timestamp":1740144148960,"version":"3.37.3"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,4,14]],"date-time":"2022-04-14T00:00:00Z","timestamp":1649894400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,4,14]],"date-time":"2022-04-14T00:00:00Z","timestamp":1649894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The phenomenon of restlessness, agitation, or cognitive disturbances experienced by dying patients is well-known in palliative care; more than half of these patients will experience delirium symptoms at end-of-life. When not identified early and effectively managed, delirium symptoms could lead to caregiver and patient distress and harm.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Eighty patients with a prognosis of 7\u2009days or less will be recruited for an open-label randomised control trial. The two arms compare oral-transmucosal haloperidol 2.5\u2009mg vs olanzapine 5\u2009mg over 72\u2009h. The severity of agitation, delirium and toxicities of treatments will be compared at the 24th, 48th and 72nd hour after drug administration.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>This trial is the first to compare anti-psychotics in the management of delirium at the dying stage in the home hospice setting using the oral transmucosal route. Ethical considerations, as well as recruitment procedures, are discussed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>This study was registered in <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> \u2013 identifier NCT04750395<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13063-022-06238-4","type":"journal-article","created":{"date-parts":[[2022,4,14]],"date-time":"2022-04-14T18:02:43Z","timestamp":1649959363000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An open-label clinical trial of oral transmucosal haloperidol and oral transmucosal olanzapine in the treatment of terminal delirium at home"],"prefix":"10.1186","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2670-3479","authenticated-orcid":false,"given":"Xiao-Juan","family":"Lyu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian David","family":"Kan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Poh-Heng","family":"Chong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keegan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yung-Hua","family":"Koh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Zheng","family":"Yeo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,4,14]]},"reference":[{"issue":"1","key":"6238_CR1","doi-asserted-by":"publisher","first-page":"32","DOI":"10.7326\/0003-4819-135-1-200107030-00011","volume":"135","author":"DJ Casarett","year":"2001","unstructured":"Casarett DJ, Inouye SK. Diagnosis and management of delirium near the end of life. Ann Intern Med. 2001;135(1):32\u201340. https:\/\/doi.org\/10.7326\/0003-4819-135-1-200107030-00011.","journal-title":"Ann Intern Med."},{"issue":"2","key":"6238_CR2","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1176\/appi.psy.45.2.107","volume":"45","author":"T Morita","year":"2004","unstructured":"Morita T, Hirai K, Sakaguchi Y, Tsuneto S, Shima Y. Family-perceived distress from delirium-related symptoms of terminally ill cancer patients. Psychosomatics. 2004;45(2):107\u201313. https:\/\/doi.org\/10.1176\/appi.psy.45.2.107.","journal-title":"Psychosomatics."},{"key":"6238_CR3","doi-asserted-by":"publisher","unstructured":"Finucane AM, Jones L, Leurent B, Sampson EL, Stone P, Tookman A, et al. Drug therapy for delirium in terminally ill adults. Cochrane Database Syst Rev. 2020;(1):CD004770. https:\/\/doi.org\/10.1002\/14651858.CD004770.pub3. Accessed 06 Apr 2022.","DOI":"10.1002\/14651858.CD004770.pub3"},{"issue":"4","key":"6238_CR4","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1097\/SPC.0000000000000236","volume":"10","author":"D Hui","year":"2016","unstructured":"Hui D, Dev R, Bruera E. Neuroleptics in the management of delirium in patients with advanced cancer. Curr Opin Support Palliat Care. 2016;10(4):316\u201323. https:\/\/doi.org\/10.1097\/SPC.0000000000000236.","journal-title":"Curr Opin Support Palliat Care."},{"issue":"2","key":"6238_CR5","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.jpainsymman.2014.05.009","volume":"48","author":"SH Bush","year":"2014","unstructured":"Bush SH, Leonard MM, Agar M, Spiller JA, Hosie A, Wright DK, et al. End-of-life delirium: issues regarding recognition, optimal management, and the role of sedation in the dying phase. J Pain Symptom Manage. 2014;48(2):215\u201330. https:\/\/doi.org\/10.1016\/j.jpainsymman.2014.05.009.","journal-title":"J Pain Symptom Manage."},{"key":"6238_CR6","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington DC: American psychiatric association; 2013.","DOI":"10.1176\/appi.books.9780890425596"},{"key":"6238_CR7","unstructured":"Singapore Statutes Online. Mental Capacity Act (Chapter 177A). Singapore: Attorney-General\u2019s Chambers of Singapore; 2010. https:\/\/sso.agc.gov.sg\/Act\/MCA2008. Accessed 6 Apr 2022."},{"issue":"5","key":"6238_CR8","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1089\/jpm.2012.0422","volume":"16","author":"M Agar","year":"2013","unstructured":"Agar M, Ko DN, Sheehan C, Chapman M, Currow DC. Informed consent in palliative care clinical trials: challenging but possible. J Palliat Med. 2013;16(5):485\u201391. https:\/\/doi.org\/10.1089\/jpm.2012.0422.","journal-title":"J Palliat Med."},{"key":"6238_CR9","unstructured":"Ministry of Health. Human Biomedical Research Act 2015. https:\/\/sso.agc.gov.sg\/Act\/HBRA2015. Accessed 6 Apr 2022."},{"issue":"4","key":"6238_CR10","doi-asserted-by":"publisher","first-page":"451","DOI":"10.4103\/psychiatry.IndianJPsychiatry_59_17","volume":"59","author":"R Jain","year":"2017","unstructured":"Jain R, Arun P, Sidana A, Sachdev A. Comparison of efficacy of haloperidol and olanzapine in the treatment of delirium. Indian J Psychiatry. 2017;59(4):451\u20136. https:\/\/doi.org\/10.4103\/psychiatry.IndianJPsychiatry_59_17.","journal-title":"Indian J Psychiatry."},{"issue":"4","key":"6238_CR11","first-page":"346","volume":"19","author":"CJ Lin","year":"2008","unstructured":"Lin CJ, Sun FJ, Fang CK, Chen HW, Lai YL. An open trial comparing haloperidol with olanzapine for the treatment of delirium in palliative and hospice center cancer patients. J Internal Med Taiwan. 2008;19(4):346\u201354.","journal-title":"J Internal Med Taiwan."},{"issue":"4","key":"6238_CR12","first-page":"13","volume":"20","author":"RE Fargason","year":"2021","unstructured":"Fargason RE, Birur B. Switching antipsychotics: A guide to dose equivalents. Curr Psychiatr. 2021;20(4):13\u20134.","journal-title":"Curr Psychiatr"},{"issue":"3","key":"6238_CR13","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/S0885-3924(96)00316-8","volume":"13","author":"W Breitbart","year":"1997","unstructured":"Breitbart W, Rosenfeld B, Roth A, Smith MJ, Cohen K, Passik S. The Memorial Delirium Assessment Scale. J Pain Symp Manage. 1997;13(3):128\u201337. https:\/\/doi.org\/10.1016\/S0885-3924(96)00316-8.","journal-title":"J Pain Symp Manage."},{"key":"6238_CR14","doi-asserted-by":"publisher","unstructured":"Lawlor PG, Nekolaichuk C, Gagnon B, Mancini IL, Pereira JL, Bruera ED. Clinical utility, factor analysis, and further validation of the memorial delirium assessment scale in patients with advanced cancer: Assessing delirium in advanced cancer. Cancer. 2000;88(12):2859\u201367. https:\/\/doi.org\/10.1002\/1097-0142(20000615)88:12&lt;2859::AID-CNCR29&gt;3.0.CO;2-T.","DOI":"10.1002\/1097-0142(20000615)88:12&lt;2859::AID-CNCR29&gt;3.0.CO;2-T"},{"issue":"1","key":"6238_CR15","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/1472-684X-13-17","volume":"13","author":"SH Bush","year":"2014","unstructured":"Bush SH, Grassau PA, Yarmo MN, Zhang T, Zinkie SJ, Pereira JL. The Richmond Agitation-Sedation Scale modified for palliative care inpatients (RASS-PAL): a pilot study exploring validity and feasibility in clinical practice. BMC Palliative Care. 2014;13(1):17. https:\/\/doi.org\/10.1186\/1472-684X-13-17.","journal-title":"BMC Palliative Care."},{"issue":"10","key":"6238_CR16","doi-asserted-by":"publisher","first-page":"2246","DOI":"10.1002\/cncr.31312","volume":"124","author":"D Hui","year":"2018","unstructured":"Hui D, Hess K, Dibaj SS, Arthur J, Dev R, Dalal S, et al. The minimal clinically important difference of the Richmond Agitation-Sedation Scale in patients with cancer with agitated delirium. Cancer. 2018;124(10):2246\u201352. https:\/\/doi.org\/10.1002\/cncr.31312.","journal-title":"Cancer."},{"key":"6238_CR17","unstructured":"National Cancer Institute, National Institutes of Health, US Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0. NIH publication 09-7473. 2009. Revised June14, 2010. https:\/\/ctep.cancer.gov\/protocoldevelopment\/electronic_applications\/docs\/ctcae_v5_quick_reference_5x7.pdf. Accessed 6 Apr 2022."}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-022-06238-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-022-06238-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-022-06238-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,16]],"date-time":"2022-04-16T02:07:22Z","timestamp":1650074842000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-022-06238-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,14]]},"references-count":17,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["6238"],"URL":"https:\/\/doi.org\/10.1186\/s13063-022-06238-4","relation":{},"ISSN":["1745-6215"],"issn-type":[{"type":"electronic","value":"1745-6215"}],"subject":[],"published":{"date-parts":[[2022,4,14]]},"assertion":[{"value":"8 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was reviewed and approved by the Agency for Integrated Care Institutional Review Board (AIC-IRB). Clinical Trial Authorisation is pending from the Health Sciences Authority Singapore (HSA).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate {24}"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication {32}"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests {28}"}}],"article-number":"311"}}