{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T06:29:05Z","timestamp":1793946545772,"version":"4.8.0"},"reference-count":30,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010377","name":"National Institute for Health and Care Excellence","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010377","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","thelancet.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["eClinicalMedicine"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1016\/j.eclinm.2026.103757","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:16:58Z","timestamp":1771892218000},"page":"103757","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"special_numbering":"C","title":["Zegocractin for acute pancreatitis with systemic inflammatory response syndrome: a randomized, controlled, dose-ranging, phase 2b trial"],"prefix":"10.1016","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6600-562X","authenticated-orcid":false,"given":"Robert","family":"Sutton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramod K.","family":"Garg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Suresh","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Buxbaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathew","family":"Philip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Stauderman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudarshan","family":"Hebbar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bechien U.","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Frank","family":"Peacock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy B.","family":"Gardner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"3","key":"10.1016\/j.eclinm.2026.103757_bib1","doi-asserted-by":"crossref","first-page":"419","DOI":"10.14309\/ajg.0000000000002645","article-title":"American College of Gastroenterology Guidelines: management of acute pancreatitis","volume":"119","author":"Tenner","year":"2024","journal-title":"Am J Gastroenterol"},{"issue":"4","key":"10.1016\/j.eclinm.2026.103757_bib2","first-page":"Cd011384","article-title":"Pharmacological interventions for acute pancreatitis","volume":"4","author":"Moggia","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"issue":"7","key":"10.1016\/j.eclinm.2026.103757_bib3","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1053\/j.gastro.2018.11.081","article-title":"Genetics, cell biology, and pathophysiology of pancreatitis","volume":"156","author":"Mayerle","year":"2019","journal-title":"Gastroenterology"},{"issue":"7","key":"10.1016\/j.eclinm.2026.103757_bib4","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1053\/j.gastro.2018.12.041","article-title":"Organ failure due to systemic injury in acute pancreatitis","volume":"156","author":"Garg","year":"2019","journal-title":"Gastroenterology"},{"issue":"10252","key":"10.1016\/j.eclinm.2026.103757_bib5","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/S0140-6736(20)31310-6","article-title":"Acute pancreatitis","volume":"396","author":"Boxhoorn","year":"2020","journal-title":"Lancet"},{"issue":"8981","key":"10.1016\/j.eclinm.2026.103757_bib6","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/S0140-6736(95)91695-4","article-title":"Is an elevated concentration of acinar cytosolic free ionised calcium the trigger for acute pancreatitis?","volume":"346","author":"Ward","year":"1995","journal-title":"Lancet"},{"issue":"8","key":"10.1016\/j.eclinm.2026.103757_bib7","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/s41575-019-0158-2","article-title":"New insights into acute pancreatitis","volume":"16","author":"Lee","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"4","key":"10.1016\/j.eclinm.2026.103757_bib8","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1152\/physrev.00003.2021","article-title":"The roles of calcium and ATP in the physiology and pathology of the exocrine pancreas","volume":"101","author":"Petersen","year":"2021","journal-title":"Physiol Rev"},{"key":"10.1016\/j.eclinm.2026.103757_bib9","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev-immunol-032414-112212","article-title":"Ion channels in innate and adaptive immunity","volume":"33","author":"Feske","year":"2015","journal-title":"Annu Rev Immunol"},{"issue":"2","key":"10.1016\/j.eclinm.2026.103757_bib10","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1053\/j.gastro.2015.04.015","article-title":"Inhibitors of ORAI1 prevent cytosolic calcium-associated injury of human pancreatic acinar cells and acute pancreatitis in 3 mouse models","volume":"149","author":"Wen","year":"2015","journal-title":"Gastroenterology"},{"issue":"12","key":"10.1016\/j.eclinm.2026.103757_bib11","doi-asserted-by":"crossref","first-page":"3085","DOI":"10.1113\/JP277856","article-title":"The Orai Ca(2+) channel inhibitor CM4620 targets both parenchymal and immune cells to reduce inflammation in experimental acute pancreatitis","volume":"597","author":"Waldron","year":"2019","journal-title":"J Physiol"},{"issue":"1","key":"10.1016\/j.eclinm.2026.103757_bib12","article-title":"Neutrophil-specific ORAI1 calcium channel inhibition reduces pancreatitis-associated acute lung injury","volume":"5","author":"Niu","year":"2024","journal-title":"Function (Oxf)"},{"issue":"4","key":"10.1016\/j.eclinm.2026.103757_bib13","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1097\/MPA.0000000000001793","article-title":"Auxora for the treatment of patients with acute pancreatitis and accompanying systemic inflammatory response syndrome: clinical development of a calcium release-activated calcium channel inhibitor","volume":"50","author":"Bruen","year":"2021","journal-title":"Pancreas"},{"issue":"4","key":"10.1016\/j.eclinm.2026.103757_bib14","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1053\/j.gastro.2018.01.031","article-title":"Initial medical treatment of acute pancreatitis: American Gastroenterological Association Institute Technical review","volume":"154","author":"Vege","year":"2018","journal-title":"Gastroenterology"},{"issue":"6","key":"10.1016\/j.eclinm.2026.103757_bib15","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1378\/chest.101.6.1644","article-title":"Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis","volume":"101","author":"Bone","year":"1992","journal-title":"Chest"},{"issue":"4","key":"10.1016\/j.eclinm.2026.103757_bib16","article-title":"The American neurogastroenterology and motility society gastroparesis cardinal symptom index-daily diary (ANMS GCSI-DD): psychometric evaluation in patients with idiopathic or diabetic gastroparesis","volume":"31","author":"Revicki","year":"2019","journal-title":"Neuro Gastroenterol Motil"},{"issue":"2","key":"10.1016\/j.eclinm.2026.103757_bib17","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1097\/j.pain.0000000000000375","article-title":"Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations","volume":"157","author":"Cooper","year":"2016","journal-title":"Pain"},{"issue":"3","key":"10.1016\/j.eclinm.2026.103757_bib18","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1148\/radiology.156.3.4023241","article-title":"Acute pancreatitis: prognostic value of CT","volume":"156","author":"Balthazar","year":"1985","journal-title":"Radiology"},{"issue":"7","key":"10.1016\/j.eclinm.2026.103757_bib19","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/ajg.2017.114","article-title":"Dynamic measurement of disease activity in acute pancreatitis: the pancreatitis activity scoring system","volume":"112","author":"Wu","year":"2017","journal-title":"Am J Gastroenterol"},{"issue":"21","key":"10.1016\/j.eclinm.2026.103757_bib20","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1056\/NEJMoa1404393","article-title":"Early versus on-demand nasoenteric tube feeding in acute pancreatitis","volume":"371","author":"Bakker","year":"2014","journal-title":"N Engl J Med"},{"issue":"3","key":"10.1016\/j.eclinm.2026.103757_bib21","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1111\/j.1541-0420.2005.00344.x","article-title":"Combining multiple comparisons and modeling techniques in dose-response studies","volume":"61","author":"Bretz","year":"2005","journal-title":"Biometrics"},{"issue":"10","key":"10.1016\/j.eclinm.2026.103757_bib22","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1002\/sim.6052","article-title":"Model-based dose finding under model uncertainty using general parametric models","volume":"33","author":"Pinheiro","year":"2014","journal-title":"Stat Med"},{"issue":"11","key":"10.1016\/j.eclinm.2026.103757_bib23","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1002\/(SICI)1097-0258(19990615)18:11<1341::AID-SIM129>3.0.CO;2-7","article-title":"Combining mortality and longitudinal measures in clinical trials","volume":"18","author":"Finkelstein","year":"1999","journal-title":"Stat Med"},{"issue":"2","key":"10.1016\/j.eclinm.2026.103757_bib24","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1093\/eurheartj\/ehr352","article-title":"The win ratio: a new approach to the analysis of composite endpoints in clinical trials based on clinical priorities","volume":"33","author":"Pocock","year":"2012","journal-title":"Eur Heart J"},{"issue":"1","key":"10.1016\/j.eclinm.2026.103757_bib25","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1136\/gutjnl-2012-302779","article-title":"Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus","volume":"62","author":"Banks","year":"2013","journal-title":"Gut"},{"key":"10.1016\/j.eclinm.2026.103757_bib26","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1136\/gutjnl-2024-334038","article-title":"Parecoxib sequential with imrecoxib for occurrence and remission of severe acute pancreatitis: a multicentre, double-blind, randomised, placebo-controlled trial","volume":"74","author":"Huang","year":"2025","journal-title":"Gut"},{"issue":"4","key":"10.1016\/j.eclinm.2026.103757_bib27","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/joim.13505","article-title":"Lessons from 20 years with COX-2 inhibitors: importance of dose-response considerations and fair play in comparative trials","volume":"292","author":"Stiller","year":"2022","journal-title":"J Intern Med"},{"issue":"1","key":"10.1016\/j.eclinm.2026.103757_bib28","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s13054-022-03964-8","article-title":"Auxora vs. placebo for the treatment of patients with severe COVID-19 pneumonia: a randomized-controlled clinical trial","volume":"26","author":"Bruen","year":"2022","journal-title":"Crit Care"},{"issue":"5462","key":"10.1016\/j.eclinm.2026.103757_bib29","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1136\/bmj.2.5462.627","article-title":"Treatment of acute pancreatitis with trasylol: report of a controlled therapeutic trial","volume":"2","author":"Skyring","year":"1965","journal-title":"Br Med J"},{"issue":"3","key":"10.1016\/j.eclinm.2026.103757_bib30","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/nrd.2017.244","article-title":"Impact of a five-dimensional framework on R&D productivity at AstraZeneca","volume":"17","author":"Morgan","year":"2018","journal-title":"Nat Rev Drug Discov"}],"container-title":["eClinicalMedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589537026000040?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589537026000040?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T05:46:38Z","timestamp":1793943998000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589537026000040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":30,"alternative-id":["S2589537026000040"],"URL":"https:\/\/doi.org\/10.1016\/j.eclinm.2026.103757","relation":{},"ISSN":["2589-5370"],"issn-type":[{"value":"2589-5370","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Zegocractin for acute pancreatitis with systemic inflammatory response syndrome: a randomized, controlled, dose-ranging, phase 2b trial","name":"articletitle","label":"Article Title"},{"value":"eClinicalMedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.eclinm.2026.103757","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"103757"}}