{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:30:54Z","timestamp":1783074654643,"version":"3.54.6"},"reference-count":56,"publisher":"Wiley","issue":"11-12","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK134321"],"award-info":[{"award-number":["DK134321"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with ulcerative colitis (UC) who are hospitalised for acute severe flares represent a high\u2010risk orphan population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To provide guidance for clinical trial design methodology in these patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We created a multi\u2010centre consortium to design and conduct a clinical trial for a novel therapeutic intervention (hyperbaric oxygen therapy) in patients with UC hospitalised for moderate\u2013severe flares. During planning, we identified and addressed specific gaps for inclusion\/exclusion criteria; disease activity measures; pragmatic trial design considerations within care pathways for hospitalised patients; standardisation of care delivery; primary and secondary outcomes; and sample size and statistical analysis approaches.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The Truelove\u2010Witt criteria should not be used in isolation. Endoscopy is critical for defining eligible populations. Patient\u2010reported outcomes should include rectal bleeding and stool frequency, with secondary measurement of urgency and nocturnal bowel movements. Trial design needs to be tailored to care pathways, with early intervention focused on replacing and\/or optimising responsiveness to steroids and later interventions focused on testing novel rescue agents or strategies. The PRECIS\u20102 framework offers a means of tailoring to local populations. We provide standardisation of baseline testing, venous thromboprophylaxis, steroid dosing, discharge criteria and post\u2010discharge follow\u2010up to avoid confounding by usual care variability. Statistical considerations are provided given the small clinical trial nature of this population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We provide an outline for framework decisions made for the hyperbaric oxygen trial in patients hospitalised for UC flares. Future research should focus on the remaining gaps identified.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.18326","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T07:48:11Z","timestamp":1728978491000},"page":"1512-1524","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Clinical Trial Design Considerations for Hospitalised Patients With Ulcerative Colitis Flares and Application to Study Hyperbaric Oxygen Therapy in the <scp>NIDDK HBOT<\/scp>\u2010<scp>UC<\/scp> Consortium"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9514-2321","authenticated-orcid":false,"given":"Parambir S.","family":"Dulai","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren Balmert","family":"Bonner","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Division of Biostatistics Northwestern University  Chicago Illinois USA"},{"name":"Northwestern University Data Analysis and Coordinating Center (NUDACC)  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Sadler","sequence":"additional","affiliation":[{"name":"Division of Hyperbaric Medicine, Department of Emergency Medicine University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5267-2592","authenticated-orcid":false,"given":"Laura E.","family":"Raffals","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gursimran","family":"Kochhar","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Alleghany Health  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lindholm","sequence":"additional","affiliation":[{"name":"Division of Hyperbaric Medicine, Department of Emergency Medicine University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Jay C.","family":"Buckey","sequence":"additional","affiliation":[{"name":"Hyperbaric Medicine Dartmouth Hitchcock Medical Center  Lebanon New Hampshire USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary N.","family":"Toups","sequence":"additional","affiliation":[{"name":"Hyperbaric Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libeth","family":"Rosas","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1536-8436","authenticated-orcid":false,"given":"Neeraj","family":"Narula","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Farncombe Family Digestive Health Research Institute McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1092-0033","authenticated-orcid":false,"given":"Vipul","family":"Jairath","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Schulich School of Medicine Western University  London Ontario Canada"},{"name":"Lawson Health Research Institute Western University  London Ontario Canada"},{"name":"Department of Epidemiology and Biostatistics Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6657-2763","authenticated-orcid":false,"given":"Sailish","family":"Honap","sequence":"additional","affiliation":[{"name":"School of Immunology and Microbial Sciences King's College London  UK"},{"name":"INFINY Institute Nancy University Hospital  Vand\u0153uvre\u2010l\u00e8s\u2010Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2536-6618","authenticated-orcid":false,"given":"Laurent","family":"Peyrin\u2010Biroulet","sequence":"additional","affiliation":[{"name":"INFINY Institute Nancy University Hospital  Vand\u0153uvre\u2010l\u00e8s\u2010Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce E.","family":"Sands","sequence":"additional","affiliation":[{"name":"Dr. Henry D. 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