{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:13:43Z","timestamp":1786115623176,"version":"build-2736575974"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The global incidence of severe acute pancreatitis (SAP) is increasing, yet mortality rates remain persistently high. Novel therapeutic approaches are urgently needed to improve outcomes. The aim of this study is to evaluate the efficacy of high-dose intravenous vitamin C in improving organ support-free days within the first 14\u202fdays and other clinical outcomes in patients with SAP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      This is a prospective, randomized, double-blind, multicenter clinical trial. Participants will be stratified and randomly assigned to either the HDIVC group or the control group. Data will be analyzed using SAS 9.4 with two-sided tests and a significance threshold of\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05. This study will be conduct at eight hospitals in China, including Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai General Hospital, Changhai Hospital, Sichuan Provincial People\u2019s Hospital, Chongqing Daping Hospital, The Second People\u2019s Hospital of Chengdu, Guanghan People\u2019s Hospital and Chongqing Emergency Medical Center. Eligible patients are adults (age\u202f\u2265\u202f18\u202fyears) diagnosed with severe acute pancreatitis according to 2012 Atlanta classification within 7\u202fdays of onset. HDIVC (500\u202fmg\/kg, 2\u202fg\/h) or placebo (normal saline) will be administered via central vein for 7\u202fdays. The primary outcome is organ support-free days within the first 14\u202fdays. Secondary outcomes include ICU all-cause mortality, changes in inflammatory biomarkers, and organ failure scores.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>If proven effective, the results of this trial could establish high-dose intravenous vitamin C as a cost-effective adjunctive therapy to improve survival in patients with severe acute pancreatitis and potentially inform future clinical practice guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>ClinicalTrials.gov<\/jats:ext-link>\n                      , identifier NCT06897384.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1850105","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T04:24:26Z","timestamp":1785990266000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of high-dose intravenous vitamin C on organ support-free days within the first 14\u202fdays in severe acute pancreatitis patients: a multicenter, randomized, double-blind, placebo-controlled clinical trial protocol"],"prefix":"10.3389","volume":"13","author":[{"given":"Bing","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianxian","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Emergency, Medical Center of Trauma and War Injury, Daping Hospital, Army Medical University, State Key Laboratory of Trauma and Chemical Poisoning","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengying","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Critical Care Unit, The Second People's Hospital of Chengdu, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Unit, Guanghan People's Hospital","place":["Deyang, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglong","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Emergency Intensive Care Unit, Sichuan Provincial People's Hospital","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, Chongqing University Central Hospital (Chongqing Emergency Medical Center)","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Emergency, Changhai Hospital, Naval Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihua","family":"Shen","sequence":"additional","affiliation":[{"name":"National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University","place":["Shanghai, China"]},{"name":"Department of Critical Care Unit, Shanghai Provincial Corps Hospital, Chinese People\u2019s Armed Police Forces","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglu","family":"Gui","sequence":"additional","affiliation":[{"name":"Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqi","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqiu","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weisong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency, Medical Center of Trauma and War Injury, Daping Hospital, Army Medical University, State Key Laboratory of Trauma and Chemical Poisoning","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qionghua","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Unit, The Second People's Hospital of Chengdu, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Unit, Guanghan People's Hospital","place":["Deyang, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Emergency Intensive Care Unit, Sichuan Provincial People's Hospital","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, Chongqing University Central Hospital (Chongqing Emergency Medical Center)","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meitang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency, Changhai Hospital, Naval Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruilan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Care Unit, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enqiang","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/S0140-6736(20)31310-6","article-title":"Acute pancreatitis","volume":"396","author":"Boxhoorn","year":"2020","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1053\/j.gastro.2021.09.043","article-title":"Global incidence of acute pancreatitis is increasing over time: a systematic review and meta-analysis","volume":"162","author":"Iannuzzi","year":"2022","journal-title":"Gastroenterology"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e12653","DOI":"10.1111\/sji.12653","article-title":"Evaluation of oxidative stress and antioxidant status: correlation with the severity of sepsis","volume":"87","author":"Kumar","year":"2018","journal-title":"Scand J Immunol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"852","DOI":"10.21037\/atm-19-4552","article-title":"High-dose vitamin C alleviates pancreatic injury via the NRF2\/NQO1\/HO-1 pathway in a rat model of severe acute pancreatitis","volume":"8","author":"Xu","year":"2020","journal-title":"Ann Transl Med"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"2865","DOI":"10.2147\/JIR.S415974","article-title":"High-dose vitamin C alleviates pancreatic necrosis by inhibiting platelet activation through the CXCL12\/CXCR4 pathway in severe acute pancreatitis","volume":"16","author":"Gui","year":"2023","journal-title":"J Inflamm Res"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s13613-025-01437-z","article-title":"High-dose intravenous vitamin C reduce C-reactive protein levels, fluid retention, and APACHE II scores in patients with moderately severe acute pancreatitis: a prospective, randomized, double-blinded, placebo-controlled study","volume":"15","author":"Zhao","year":"2025","journal-title":"Ann Intensive Care"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"78","DOI":"10.3945\/an.110.000109","article-title":"Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries","volume":"2","author":"Levine","year":"2011","journal-title":"Adv Nutr"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"533","DOI":"10.7326\/0003-4819-140-7-200404060-00010","article-title":"Vitamin C pharmacokinetics: implications for oral and intravenous use","volume":"140","author":"Padayatty","year":"2004","journal-title":"Ann Intern Med"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.21037\/apm-20-1387","article-title":"Beneficial aspects of high dose intravenous vitamin C on patients with COVID-19 pneumonia in severe condition: a retrospective case series study","volume":"10","author":"Zhao","year":"2021","journal-title":"Ann Palliat Med"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1097\/CM9.0000000000001746","article-title":"Potential benefit of high-dose intravenous vitamin C for coronavirus disease 2019 pneumonia","volume":"135","author":"Zhao","year":"2022","journal-title":"Chin Med J"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1186\/s13054-014-0460-x","article-title":"Vitamin C revisited","volume":"18","author":"Oudemans-van Straaten","year":"2014","journal-title":"Crit Care"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.3390\/nu13020615","article-title":"On behalf of the O: vitamin C-sources, physiological role, kinetics, deficiency, use, toxicity, and determination","volume":"13","author":"Dosed\u011bl","year":"2021","journal-title":"Nutrients"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3390\/nu9111211","article-title":"Vitamin C and immune function","volume":"9","author":"Carr","year":"2017","journal-title":"Nutrients"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.3390\/nu12123760","article-title":"Vitamin C-an adjunctive therapy for respiratory infection, sepsis and COVID-19","volume":"12","author":"Holford","year":"2020","journal-title":"Nutrients"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1186\/1472-6882-14-442","article-title":"Vitamin C treatment attenuates hemorrhagic shock related multi-organ injuries through the induction of heme oxygenase-1","volume":"14","author":"Zhao","year":"2014","journal-title":"BMC Complement Altern Med"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e99134","DOI":"10.1371\/journal.pone.0099134","article-title":"Pharmacological preconditioning with vitamin C attenuates intestinal injury via the induction of heme oxygenase-1 after hemorrhagic shock in rats","volume":"9","author":"Zhao","year":"2014","journal-title":"PLoS One"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.3748\/wjg.v9.i11.2565","article-title":"Therapeutic efficacy of high-dose vitamin C on acute pancreatitis and its potential mechanisms","volume":"9","author":"Du","year":"2003","journal-title":"World J Gastroenterol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e7586","DOI":"10.1136\/bmj.e7586","article-title":"Spirit 2013 explanation and elaboration: guidance for protocols of clinical trials","volume":"346","author":"Chan","year":"2013","journal-title":"BMJ"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3390\/nu11102412","article-title":"The pharmacokinetics of vitamin C","volume":"11","author":"Lykkesfeldt","year":"2019","journal-title":"Nutrients"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.1016\/j.chest.2018.02.025","article-title":"Vitamin C pharmacokinetics in critically ill patients: a randomized trial of four IV regimens","volume":"153","author":"de Grooth","year":"2018","journal-title":"Chest"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e620","DOI":"10.1097\/CCM.0000000000004396","article-title":"Harm of IV high-dose vitamin C therapy in adult patients: a scoping review","volume":"48","author":"Yanase","year":"2020","journal-title":"Crit Care Med"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1001\/jama.2019.11825","article-title":"Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure: the CITRIS-ALI randomized clinical trial","volume":"322","author":"Fowler","year":"2019","journal-title":"JAMA"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2387","DOI":"10.1056\/NEJMoa2200644","article-title":"Intravenous vitamin C in adults with sepsis in the intensive care unit","volume":"386","author":"Lamontagne","year":"2022","journal-title":"N Engl J Med"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/s13054-023-04392-y","article-title":"The outcome of IV vitamin C therapy in patients with sepsis or septic shock: a meta-analysis of randomized controlled trials","volume":"27","author":"Liang","year":"2023","journal-title":"Crit Care"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s13613-023-01116-x","article-title":"Intravenous vitamin C monotherapy in critically ill patients: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis","volume":"13","author":"Lee","year":"2023","journal-title":"Ann Intensive Care"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1850105\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T04:24:27Z","timestamp":1785990267000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1850105\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,6]]},"references-count":25,"alternative-id":["10.3389\/fnut.2026.1850105"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2026.1850105","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,6]]},"article-number":"1850105"}}