{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T02:47:56Z","timestamp":1768531676463,"version":"3.49.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T00:00:00Z","timestamp":1693872000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T00:00:00Z","timestamp":1693872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100013232","name":"Stiftelsen Norsk Luftambulanse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013232","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005366","name":"University of Oslo","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005366","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Pre-hospital pain management has traditionally been performed with intravenous (IV) morphine, but oligoanalgesia remain a recognized problem. Pain reduction is essential for patient satisfaction and is regarded as a measure of successful treatment. We aim to establish whether non-invasive methods such as inhalation of methoxyflurane is non-inferior to intranasal fentanyl or non-inferior to the well-known IV morphine in the pre-hospital treatment of acute pain.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Method\/design<\/jats:title>\n                <jats:p>The PreMeFen study is a phase three, three-armed, randomized, controlled, non-inferiority trial to compare three regimens of analgesics: inhalation of methoxyflurane and intranasal (IN) fentanyl versus IV morphine. It is an open-label trial with a 1:1:1 randomization to the three treatment groups. The primary endpoint is the change in pain numeric rating scale (NRS) (0\u201310) from baseline to 10\u00a0min after start of investigational medicinal product administration (IMP). The non-inferiority margin was set to 1.3, and a sample size of 270 patients per protocol (90 in each treatment arm) will detect this difference with 90% power.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>We chose a study design with comparison of analgesic regimens rather than fixed doses because of the substantial differences in drug characteristics and for the results to be relevant to inform policymakers in the pre-hospital setting. We recognize that easier administration of analgesics will lead to better pain management for many patients if the regimens are as good as the existing, and hence, we chose a non-inferiority design. The primary endpoint, the change in pain (NRS) after 10\u00a0min, is set to address the immediate need of pain reduction for patients with acute prehospital pain. On a later stage, more analgesic methods are often available.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Summary<\/jats:title>\n                <jats:p>PreMeFen is a non-inferiority randomized controlled trial comparing three analgesic regimens aiming to establish whether inhalation of methoxyflurane or intranasal fentanyl is as good as IV morphine for fast reduction of acute pain in the prehospital setting.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13063-023-07590-9","type":"journal-article","created":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T08:01:56Z","timestamp":1693900916000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparison of three regimens with inhalational methoxyflurane versus intranasal fentanyl versus intravenous morphine in pre-hospital acute pain management: study protocol for a randomized controlled trial (PreMeFen)"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5291-9375","authenticated-orcid":false,"given":"Randi","family":"Simensen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars Olav","family":"Fjose","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9519-241X","authenticated-orcid":false,"given":"Marius","family":"Rehn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4420-5588","authenticated-orcid":false,"given":"Jostein","family":"Hagemo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kjetil","family":"Thorsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9602-4370","authenticated-orcid":false,"given":"Fridtjof","family":"Heyerdahl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,9,5]]},"reference":[{"issue":"1","key":"7590_CR1","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s13049-019-0588-4","volume":"27","author":"KD Friesgaard","year":"2019","unstructured":"Friesgaard KD, Kirkegaard H, Rasmussen C-H, Giebner M, Christensen EF, Nikolajsen L. 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NCT05137184) 30 November 2021 () and EudraCT (ref. 2021\u2013000549-42). Important protocol modifications are communicated to REC, the Norwegian Medicinal Agency, which updates EudraCT, and to Clinical Trials.gov. The study will be performed in accordance with the Helsinki declaration. The study is based on the patients\u2019 oral consent, witnessed and confirmed with the EMS provider\u2019s signature in an informed consent form (ICF). For eligible patients, the EMS provider on-site reads out a predefined text to explain the nature of the study. Patients included in the study receive written study information including detailed information on how to withdraw from the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The participants oral consent includes publishing approval, and the written participant information brochure contains publication-related information.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"571"}}