{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:05:25Z","timestamp":1784693125182,"version":"3.55.0"},"reference-count":6,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["079649"],"award-info":[{"award-number":["079649"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007405","name":"Hjerteforeningen","doi-asserted-by":"publisher","award":["2023\u201012401"],"award-info":[{"award-number":["2023\u201012401"]}],"id":[{"id":"10.13039\/100007405","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Anaesthesiol Scand"],"published-print":{"date-parts":[[2026,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Post\u2010cardiac arrest care for patients resuscitated from out\u2010of\u2010hospital cardiac arrest (OHCA) includes multiple pharmacological and physiological interventions, yet optimal strategies to reduce post\u2010cardiac arrest syndrome\u2013related morbidity and mortality remain uncertain. The DANOHCA (Danish Out\u2010of\u2010Hospital Cardiac Arrest) trial evaluates four such interventions\u2014high\u2010dose dexamethasone, prophylactic olanzapine, elevated backrest position, and early wakeup\u2014in a factorial trial framework. This manuscript presents the complete statistical analysis plan for analyses common to all four DANOHCA interventions.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n DANOHCA is an investigator\u2010initiated, multicenter, randomized, 2\u2009\u00d7\u20092\u2009\u00d7\u20092\u2009\u00d7\u20092 factorial clinical trial enrolling comatose adult OHCA patients with a presumed cardiac etiology who achieve sustained return of spontaneous circulation, with randomization within 180\u2009min of return of spontaneous circulation. Participants are co\u2010randomized to Dexamethasone versus placebo, olanzapine versus placebo, backrest elevation at 35\u00b0 versus 5\u00b0, and early (\u2264\u20096\u2009h) versus late (28\u201336\u2009h) wakeup, with pharmacological interventions blinded and physiological interventions open\u2010label. This statistical analysis plan specifies the primary and secondary outcomes, covariate adjustment, handling of missing data, assessments of interactions between interventions, and assumption checks, with all primary analyses conducted according to the intention\u2010to\u2010treat principle. The analysis plan is finalized prior to completion of randomization.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The primary outcomes are 90\u2010day all\u2010cause mortality for the dexamethasone and backrest interventions, and days alive outside hospital within 30\u2009days for the olanzapine and early wakeup interventions, with common secondary and tertiary endpoints including mortality at later time points, neurological function, health\u2010related quality of life, organ function, and safety outcomes. Mixed\u2010effects regression models, Cox regression, stratified nonparametric tests, and prespecified sensitivity analyses will be applied to minimize bias and quantify intervention effects, including their associated uncertainties.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n This predefined statistical analysis plan provides a detailed, transparent framework for the primary analyses and reporting of the DANOHCA trial.<\/jats:p>\n \n Trial Registration:<\/jats:bold>\n Clinical Trials Information System (CTIS): 2024\u2010515997\u201028\u201000\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/aas.70288","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:56:23Z","timestamp":1782284183000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Danish Out\u2010of\u2010Hospital Cardiac Arrest Trial: A Statistical Analysis Plan"],"prefix":"10.1111","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2778-8075","authenticated-orcid":false,"given":"Simon","family":"M\u00f8lstr\u00f8m","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Odense University Hospital Odense Denmark"},{"name":"Department of Clinical Research, Faculty of Health Sciences University of Southern Denmark Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2873-5845","authenticated-orcid":false,"given":"Jacob E.","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Faculty of Health Sciences University of Southern Denmark Odense Denmark"},{"name":"Department of Cardiology Odense University Hospital Odense Denmark"},{"name":"Department of Cardiology, the Heart Centre Copenhagen University Hospital\u2014Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1080-3344","authenticated-orcid":false,"given":"Henrik","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Odense University Hospital Odense Denmark"},{"name":"Department of Clinical Research, Faculty of Health Sciences University of Southern Denmark Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8850-2982","authenticated-orcid":false,"given":"Anders M.","family":"Grejs","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Aarhus University Hospital Aarhus Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6149-7186","authenticated-orcid":false,"given":"Steffen","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Aarhus University Hospital Aarhus Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5244-0399","authenticated-orcid":false,"given":"Jesper","family":"Kj\u00e6rgaard","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the Heart Centre Copenhagen University Hospital\u2014Rigshospitalet Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1199-0981","authenticated-orcid":false,"given":"Christian","family":"Hassager","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the Heart Centre Copenhagen University Hospital\u2014Rigshospitalet Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6312-2457","authenticated-orcid":false,"given":"Martin A. S.","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the Heart Centre Copenhagen University Hospital\u2014Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0053-2560","authenticated-orcid":false,"given":"Lars P. K.","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health Sciences University of Copenhagen Copenhagen Denmark"},{"name":"Department of Intensive Care Zealand University Hospital, Koege Hospital K\u00f8ge Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2190-145X","authenticated-orcid":false,"given":"Bodil S.","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Aalborg University Hospital Aalborg Denmark"},{"name":"Department of Clinical Medicine, Faculty of Medicine Aalborg University Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6615-4438","authenticated-orcid":false,"given":"Jo B.","family":"Andreasen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Aalborg University Hospital Aalborg Denmark"},{"name":"Department of Clinical Medicine, Faculty of Medicine Aalborg University Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0858-4269","authenticated-orcid":false,"given":"S\u00f6ren","family":"M\u00f6ller","sequence":"additional","affiliation":[{"name":"Epidemiology, Biostatistics and Biodemography, Department of Public Health University of Southern Denmark Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-023-01871-6"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-025-08117-3"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.190652"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000003299"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-022-01564-6"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/aas.14063"}],"container-title":["Acta Anaesthesiologica Scandinavica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aas.70288","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/aas.70288","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aas.70288","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T03:44:16Z","timestamp":1784691856000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/aas.70288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":6,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/aas.70288"],"URL":"https:\/\/doi.org\/10.1111\/aas.70288","archive":["Portico"],"relation":{},"ISSN":["0001-5172","1399-6576"],"issn-type":[{"value":"0001-5172","type":"print"},{"value":"1399-6576","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]},"assertion":[{"value":"2026-04-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70288"}}