{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T03:19:46Z","timestamp":1781666386548,"version":"3.54.5"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"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"],"abstract":"<jats:title>Abstract\n<\/jats:title><jats:sec>\n                <jats:title>Background\n<\/jats:title>\n                <jats:p>Hip fractures are a source of severe pain among the elderly population and pose challenges due to limited analgesic tolerance. Perioperative methadone has shown promise in our pilot study suggesting a safe dose of 0.10\u00a0mg\/kg, prompting further investigation into its benefits for elderly hip fracture patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This study employs a double-blinded randomized controlled trial to assess the analgesic effects of a single dose of methadone during hip fracture surgery. Patients aged\u2009\u2265\u200960\u00a0years are consecutively enrolled and randomized to receive either perioperative methadone (treatment group) or a saline solution (placebo group). A sample size of 130 patients is required for 88% statistical power. The medication is administered intravenously at anesthesia induction and monitored until discharge. A follow-up observation is conducted 3\u00a0months post-surgery.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>Primary outcome: Daily consumption of opioids within the first 3\u00a0days after surgery. Secondary outcomes include pain, mobility, nausea, vomiting, time to discharge, need for antidote, delirium, and constipation. The 3-month follow-up includes opioid use, pain, EQ-5D-5L scores, mobility, and persistent side effects. If statistically significant advantages are found in the treatment group, perioperative methadone could be considered as standard care for hip fracture patients, potentially enhancing their pain management. The study\u2019s outcomes will provide insights into the feasibility and effectiveness of incorporating methadone into routine clinical practices for this patient group.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>ClinicalTrials.gov ID: NCT06086171, submitted 4. October 2023. EU-CT: 2023\u2013506252-24\u201300, UTN: U1111-1294\u20136125.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13063-024-08694-6","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T10:52:51Z","timestamp":1734691971000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Perioperative methadone compared to placebo in elderly hip fracture patients: a study protocol for a randomized controlled trial (MetaHip trial)"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9205-2005","authenticated-orcid":false,"given":"Kevin Heeb\u00f8ll","family":"Nygaard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Str\u00f8m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Specht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofie Ronja","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper Ougaard","family":"Sch\u00f8nnemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"issue":"1","key":"8694_CR1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.4103\/0019-5413.73656","volume":"45","author":"DK Dhanwal","year":"2011","unstructured":"Dhanwal DK, Dennison EM, Harvey NC, Cooper C. Epidemiology of hip fracture: Worldwide geographic variation. Indian J Orthop. 2011;45(1):15\u201322.","journal-title":"Indian J Orthop"},{"issue":"10","key":"8694_CR2","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1007\/s11916-019-0814-9","volume":"23","author":"A Dizdarevic","year":"2019","unstructured":"Dizdarevic A, Farah F, Ding J, Shah S, Bryan A, Kahn M, et al. A comprehensive review of analgesia and pain modalities in hip fracture pathogenesis. Curr Pain Headache Rep. 2019;23(10):72.","journal-title":"Curr Pain Headache Rep"},{"issue":"4","key":"8694_CR3","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/S0885-3924(00)00113-5","volume":"19","author":"RS Morrison","year":"2000","unstructured":"Morrison RS, Siu AL. A comparison of pain and its treatment in advanced dementia and cognitively intact patients with hip fracture. J Pain Symptom Manage. 2000;19(4):240\u20138.","journal-title":"J Pain Symptom Manage"},{"issue":"2","key":"8694_CR4","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1080\/17453674.2018.1428436","volume":"89","author":"C Jantzen","year":"2018","unstructured":"Jantzen C, Madsen CM, Lauritzen JB, J\u00f8rgensen HL. Temporal trends in hip fracture incidence, mortality, and morbidity in Denmark from 1999 to 2012. Acta Orthop. 2018;89(2):170\u20136.","journal-title":"Acta Orthop"},{"key":"8694_CR5","doi-asserted-by":"publisher","first-page":"637","DOI":"10.2147\/CIA.S1939","volume":"2","author":"G McCleane","year":"2008","unstructured":"McCleane G. Pharmacological pain management in the elderly patient. Clin Interv Aging. 2008;2:637\u201343.","journal-title":"Clin Interv Aging"},{"key":"8694_CR6","first-page":"2","volume":"180","author":"P Uhrbrand","year":"2018","unstructured":"Uhrbrand P, Simoni AH, Olesen AE, Pedersen AB, Christiansen CF, Nikolajsen L. Morfinafh\u00e6ngighed som komplikation i forbindelse med kirurgi. Ugeskr Laeger. 2018;180:2\u20135.","journal-title":"Ugeskr Laeger"},{"key":"8694_CR7","doi-asserted-by":"publisher","unstructured":"Pectol RW, Kavolus MW, Kiefer A. et al. Comparison of post-op opioid use and pain between short and long cephalomedullary nails in elderly intertrochanteric fractures. Eur J Orthop Surg Traumatol. 2023;33:3135\u201341. https:\/\/doi.org\/10.1007\/s00590-023-03553-7.","DOI":"10.1007\/s00590-023-03553-7"},{"issue":"7S","key":"8694_CR8","doi-asserted-by":"publisher","first-page":"S530","DOI":"10.1016\/j.arth.2022.01.071","volume":"37","author":"TE Hereford","year":"2022","unstructured":"Hereford TE, Porter A 3rd, Stambough JB, Cherney SM, Mears SC. Prevalence of chronic opioid use in the elderly after hip fracture surgery. J Arthroplasty. 2022;37(7S):S530\u20135.","journal-title":"J Arthroplasty"},{"issue":"1","key":"8694_CR9","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1097\/00000542-198407000-00005","volume":"61","author":"K Gourlay Geoffrey","year":"1984","unstructured":"Gourlay Geoffrey K, Pharm B, Willis Richard J, Wilson PR. Postoperative pain control with methadone: influence of supplementary methadone doses and blood concentration\u2014response relationships. Anesthesiology. 1984;61(1):19\u201326.","journal-title":"Anesthesiology"},{"key":"8694_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/6974321","volume":"2020","author":"MC Kendall","year":"2020","unstructured":"Kendall MC, Alves LJ, Pence K, Mukhdomi T, Croxford D, De Oliveira GS. The effect of intraoperative methadone compared to morphine on postsurgical pain: a meta-analysis of randomized controlled trials. 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Perioperative care in adults: surgery and opioids best practice guidelines. London: Faculty of Pain Medicine; 2021. Available from: https:\/\/fpm.ac.uk\/sites\/fpm\/files\/documents\/2021-03\/surgery-and-opioids-2021_4.pdf."},{"key":"8694_CR17","doi-asserted-by":"publisher","first-page":"101228","DOI":"10.1016\/j.conctc.2023.101228","volume":"36","author":"AK Pedersen","year":"2023","unstructured":"Pedersen AK, Nygaard KH, Petersen SR, Specht K, Str\u00f8m T, Moos CM, et al. Adjusting perioperative methadone dose for elderly and fragile hip fracture patients (MetaHip-trial) \u2013 A statistical analysis plan for an adaptive dose-finding trial. Contemp Clin Trials Commun. 2023;36:101228.","journal-title":"Contemp Clin Trials Commun"},{"issue":"3","key":"8694_CR18","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/0376-8716(80)90180-5","volume":"5","author":"MJ Kreek","year":"1980","unstructured":"Kreek MJ, Schecter AJ, Gutjahr CL, Hecht M. 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BMJ. 2013;346(15):e7586-e.","journal-title":"BMJ"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-024-08694-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-024-08694-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-024-08694-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T11:04:45Z","timestamp":1734692685000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-024-08694-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,20]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["8694"],"URL":"https:\/\/doi.org\/10.1186\/s13063-024-08694-6","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,20]]},"assertion":[{"value":"29 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 December 2024","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 present study will be conducted according to the Helsinki II declaration, the Danish Health Act, and The Act on Processing of Personal Data. Approval of the study will be sought using CTIS seeing that it is a clinical trial involving medical drugs. This definition is written and updated by The Danish Medicine Agency and can be found on their website. The Danish Medicine Agency and the National Committee on Health Research Ethics are applied for approval simultaneously in CTIS. Furthermore, the study needs to be approved by The Danish Data Protection Agency. The principal investigator will inform the National Committee on Health Research Ethics and The Danish Medicine Agency if any significant changes are made to the protocol. The project is also registered on ClinicalTrials.gov. The study will only be initiated when all relevant approvals have been granted and the initiation visit by the GCP unit has been completed.Any participating patient must provide informed both oral and written consent before inclusion. The principal investigator or sub-investigator is obligated to inform patients of any aspects regarding participation in the study. All data will be treated confidentially. Any involved personnel is subject to professional secrecy. Reporting of study data will be anonymized using patient study numbers which will be assigned upon inclusion. The sponsor and principal investigator assure direct access to data or documents and allow monitoring, auditing, and inspections from The Danish Medicine Agency and GCP unit. The principal investigator ensures that the study meets GCP criteria. The authors declare no conflict of interest and regardless of the study outcome, the results will be published in an internationally recognized peer-reviewed medical journal.The inclusion of patients meets the criteria regarding the rights of a subject as written by the National Committee on Health Research Ethics. Patients must provide both oral and written informed consent before inclusion and are informed of their right to have an assessor. They are informed of any aspects of the study which also include risks and side effects. They will be given 2\u00a0h of consideration before consent is obtained. Patients receive information from and are recruited by orthopedic doctors. Furthermore, consent to participation can be withdrawn at any time without affecting the patient or the quality of treatment. Patients can obtain insight to study results after completion if they tick off the field regarding study results in the statement of consent. Any patient who has ticked off the field will receive a link to the final publication through a message in e-Boks.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate {24}"}},{"value":"By submitting this protocol for publication, the authors hereby consent to the dissemination and publication of the protocol, including all its contents, in the chosen journal or other publication medium. The authors acknowledge that the protocol contains details of a randomized controlled trial (RCT) and understand that publication of this protocol may lead to the dissemination of sensitive or confidential information related to the trial, including study design, intervention methods, outcome measures, and data analysis plans.The authors grant permission to the journal or publication medium to reproduce, distribute, and publicly display the protocol, in whole or in part, in print or electronic format, including but not limited to publication in online repositories, databases, and indexing services. Furthermore, the authors affirm that they have obtained all necessary permissions, approvals, and clearances required for the publication of this protocol, including any ethical approvals from relevant ethics committees, and have complied with all applicable regulations and guidelines governing the conduct of clinical trials and publication of trial protocols.The authors understand that publication of the protocol does not imply acceptance or endorsement of the study findings and that subsequent publication of trial results will be subject to separate review and editorial processes. We can provide a model consent form on request.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication {32}"}},{"value":"All authors declare no competing interests. Study personnel and site had no economic interests in completing the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests {28}"}}],"article-number":"842"}}