{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:12:06Z","timestamp":1792807926273,"version":"4.5.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"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>\n          <jats:sec>\n            <jats:title>Background\n<\/jats:title>\n            <jats:p>Patients undergoing invasive mechanical ventilation often require pharmacologic sedation to facilitate tolerance of this life-sustaining intervention, but sedatives currently used in routine care have substantial limitations. Isoflurane is an inhaled volatile anesthetic with pharmacologic properties potentially suitable to sedation of ventilator-dependent critically ill patients, but need for specialized drug administration equipment has limited its use historically to general anesthesia in the operating theatre. This trial will evaluate isoflurane, administered using a novel drug delivery system, for sedation of ventilator-dependent adult intensive care unit (ICU) patients in the United States (US).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>The Inhaled Sedation versus Propofol in Respiratory Failure in the ICU (INSPiRE-ICU2) is a phase 3, multicenter, randomized, controlled, assessor-blinded non-inferiority trial that will evaluate efficacy and safety of inhaled isoflurane delivered via the Sedaconda ACD-S, compared to intravenous propofol, for sedation of mechanically ventilated adult ICU patients. At 16 US hospitals, 235 enrolled patients requiring continuous sedation during invasive mechanical ventilation will be randomized in 1.5:1 ratio to inhaled isoflurane or intravenous propofol for sedation. Treatment duration is expected to be at least 12\u00a0h and may last up to 48 (\u00b1\u20096) h or until no longer needing continuous sedation, whichever occurs first. The primary endpoint is the percentage of time sedation depth is maintained within the targeted range (Richmond Agitation Sedation Scale\u2009\u2212\u20091 to\u2009\u2212\u20094), in the absence of rescue sedation, during the treatment period. Secondary superiority outcomes include opioid exposure, wake-up time, cognitive recovery after end-of-treatment, and preservation of spontaneous breathing effort.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Discussion<\/jats:title>\n            <jats:p>The INSPiRE-ICU2 trial will help determine the potential role of isoflurane for sedation of ventilator-dependent adult patients in the ICU. Key trial design features, including adoption of the estimand framework and blinded assessments of sedation depth, pain, and cognitive recovery, will ensure a rigorous evaluation of isoflurane for ICU sedation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Trial\u00a0registration<\/jats:title>\n            <jats:p>ClinicalTrials.gov, NCT05327296. First registered on April 5, 2022.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13063-025-08791-0","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T07:29:41Z","timestamp":1743406181000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Inhaled sedation versus propofol in respiratory failure in the ICU (INSPiRE-ICU2): study protocol for a multicenter randomized controlled trial"],"prefix":"10.1186","volume":"26","author":[{"given":"Brian","family":"O\u2019Gara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7366-1350","authenticated-orcid":false,"given":"Alexis L.","family":"Serra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1257-2239","authenticated-orcid":false,"given":"Joshua A.","family":"Englert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6501-1390","authenticated-orcid":false,"given":"Alisha","family":"Sachdev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Owens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7365-5265","authenticated-orcid":false,"given":"Steven Y.","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5972-4340","authenticated-orcid":false,"given":"Pauline K.","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Talmor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Sverud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Sackey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0797-2374","authenticated-orcid":false,"given":"Jeremy R.","family":"Beitler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"key":"8791_CR1","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1097\/CCM.0b013e318298a139","volume":"41","author":"H Wunsch","year":"2013","unstructured":"Wunsch H, Wagner J, Herlim M, Chong DH, Kramer AA, Halpern SD. 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Written informed consent will be obtained prior to enrollment from each participant or their legally authorized representative. A representative example of a consent form is included as Additional File 2. Consent forms include language that is specific to each site in accordance with local law and institutional policies.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"BO and DT receive consulting fees from Sedana Medical for participation on the scientific advisory board. ALS and JRB have received compensation from Columbia University for their work on the trial. JRB previously received consulting fees from Sedana Medical for support with trial design but ended any direct financial relationship prior to initiating the trial. IS and PS are employed by Sedana Medical. All other authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"114"}}