D. Clark Files MD , Michael A. Matthay MD , Lorraine B. Ware MD , Roy G. Brower MD , Neil R. Aggarwal MD , Samuel M. Brown MD , Steven Y. Chang MD , Ivor S. Douglas MD , Abhijit Duggal MD , Kevin W. Gibbs MD , Scott Fields PharmD , Andrea S. Foulkes ScD , Adit Ginde MD , Andrew Goodwin MD , Estelle S. Harris MD , Gregory W. Hendey MD , Kathryn Hibbert MD , R.Duncan Hite MD , Catherine L. Hough MD , Weixing Huang MSPH , Alpha A. Fowler MD
{"title":"抗坏血酸治疗重症败血症患者器官功能障碍","authors":"D. Clark Files MD , Michael A. Matthay MD , Lorraine B. Ware MD , Roy G. Brower MD , Neil R. Aggarwal MD , Samuel M. Brown MD , Steven Y. Chang MD , Ivor S. Douglas MD , Abhijit Duggal MD , Kevin W. Gibbs MD , Scott Fields PharmD , Andrea S. Foulkes ScD , Adit Ginde MD , Andrew Goodwin MD , Estelle S. Harris MD , Gregory W. Hendey MD , Kathryn Hibbert MD , R.Duncan Hite MD , Catherine L. Hough MD , Weixing Huang MSPH , Alpha A. Fowler MD","doi":"10.1016/j.chstcc.2025.100168","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>A phase 2 trial of high-dose IV ascorbate suggested reduced mortality in patients with ARDS, although trials in sepsis have failed to show clinical benefit.</div></div><div><h3>Research Question</h3><div>Does IV high-dose ascorbate improve outcomes in patients with sepsis at risk of or with ARDS?</div></div><div><h3>Study Design and Methods</h3><div>In this phase 2b multicenter randomized placebo-controlled trial, patients with known or suspected infection and either shock or acute hypoxemic respiratory failure were randomized to ascorbate (50 mg/kg IV every 6 hours for 5 days) or a matching placebo. The primary outcome was days alive and free of respiratory, renal, and circulatory organ support to day 28. Secondary outcomes included clinical and biological end points.</div></div><div><h3>Results</h3><div>After enrolling 79 participants, the trial was terminated because of the publication of a separate study of septic shock reporting increased mortality with ascorbate. In the current study, days free of organ support were not different for patients receiving ascorbate compared with those receiving placebo: mean (SD), 20.5 (9.5) days vs 19.0 (10.8) days, respectively (<em>P</em> = .528). The 90-day all-cause mortality was 15% in the ascorbate group vs 33% in the placebo group (<em>P</em> = .057). This was 1 of 19 secondary end points. Soluble tumor necrosis factor receptor 1 levels were reduced in the ascorbate group vs placebo from baseline to both day 2 (median, –861 pg/mL [interquartile range (IQR), –3,043 to 128.9 pg/mL] vs 241.4 pg/mL [–820 to 1,671 pg/mL]; <em>P</em> = .005) and day 3 (median, –1,511 pg/mL [IQR, –2,636 to –36.3 pg/mL] vs –131 pg/mL [–986 to 2,202 pg/mL]; <em>P</em> = .008).</div></div><div><h3>Interpretation</h3><div>Ascorbate did not improve days free of organ failure, although no safety concerns were identified in this small study. Ascorbate was shown to reduce a biological marker of inflammation associated with adverse outcomes in sepsis and lung injury.</div></div><div><h3>Clinical Trial Registration</h3><div>ClinicalTrials.gov; No.: NCT04291508; URL: <span><span>www.clinicaltrials.gov</span><svg><path></path></svg></span></div></div>","PeriodicalId":93934,"journal":{"name":"CHEST critical care","volume":"3 3","pages":"Article 100168"},"PeriodicalIF":0.0000,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ascorbate for Organ Dysfunction in Critically Ill Patients With Sepsis\",\"authors\":\"D. Clark Files MD , Michael A. Matthay MD , Lorraine B. Ware MD , Roy G. Brower MD , Neil R. Aggarwal MD , Samuel M. Brown MD , Steven Y. Chang MD , Ivor S. Douglas MD , Abhijit Duggal MD , Kevin W. Gibbs MD , Scott Fields PharmD , Andrea S. Foulkes ScD , Adit Ginde MD , Andrew Goodwin MD , Estelle S. Harris MD , Gregory W. Hendey MD , Kathryn Hibbert MD , R.Duncan Hite MD , Catherine L. Hough MD , Weixing Huang MSPH , Alpha A. Fowler MD\",\"doi\":\"10.1016/j.chstcc.2025.100168\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>A phase 2 trial of high-dose IV ascorbate suggested reduced mortality in patients with ARDS, although trials in sepsis have failed to show clinical benefit.</div></div><div><h3>Research Question</h3><div>Does IV high-dose ascorbate improve outcomes in patients with sepsis at risk of or with ARDS?</div></div><div><h3>Study Design and Methods</h3><div>In this phase 2b multicenter randomized placebo-controlled trial, patients with known or suspected infection and either shock or acute hypoxemic respiratory failure were randomized to ascorbate (50 mg/kg IV every 6 hours for 5 days) or a matching placebo. The primary outcome was days alive and free of respiratory, renal, and circulatory organ support to day 28. Secondary outcomes included clinical and biological end points.</div></div><div><h3>Results</h3><div>After enrolling 79 participants, the trial was terminated because of the publication of a separate study of septic shock reporting increased mortality with ascorbate. In the current study, days free of organ support were not different for patients receiving ascorbate compared with those receiving placebo: mean (SD), 20.5 (9.5) days vs 19.0 (10.8) days, respectively (<em>P</em> = .528). The 90-day all-cause mortality was 15% in the ascorbate group vs 33% in the placebo group (<em>P</em> = .057). This was 1 of 19 secondary end points. Soluble tumor necrosis factor receptor 1 levels were reduced in the ascorbate group vs placebo from baseline to both day 2 (median, –861 pg/mL [interquartile range (IQR), –3,043 to 128.9 pg/mL] vs 241.4 pg/mL [–820 to 1,671 pg/mL]; <em>P</em> = .005) and day 3 (median, –1,511 pg/mL [IQR, –2,636 to –36.3 pg/mL] vs –131 pg/mL [–986 to 2,202 pg/mL]; <em>P</em> = .008).</div></div><div><h3>Interpretation</h3><div>Ascorbate did not improve days free of organ failure, although no safety concerns were identified in this small study. Ascorbate was shown to reduce a biological marker of inflammation associated with adverse outcomes in sepsis and lung injury.</div></div><div><h3>Clinical Trial Registration</h3><div>ClinicalTrials.gov; No.: NCT04291508; URL: <span><span>www.clinicaltrials.gov</span><svg><path></path></svg></span></div></div>\",\"PeriodicalId\":93934,\"journal\":{\"name\":\"CHEST critical care\",\"volume\":\"3 3\",\"pages\":\"Article 100168\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-05-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CHEST critical care\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2949788425000413\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CHEST critical care","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2949788425000413","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Ascorbate for Organ Dysfunction in Critically Ill Patients With Sepsis
Background
A phase 2 trial of high-dose IV ascorbate suggested reduced mortality in patients with ARDS, although trials in sepsis have failed to show clinical benefit.
Research Question
Does IV high-dose ascorbate improve outcomes in patients with sepsis at risk of or with ARDS?
Study Design and Methods
In this phase 2b multicenter randomized placebo-controlled trial, patients with known or suspected infection and either shock or acute hypoxemic respiratory failure were randomized to ascorbate (50 mg/kg IV every 6 hours for 5 days) or a matching placebo. The primary outcome was days alive and free of respiratory, renal, and circulatory organ support to day 28. Secondary outcomes included clinical and biological end points.
Results
After enrolling 79 participants, the trial was terminated because of the publication of a separate study of septic shock reporting increased mortality with ascorbate. In the current study, days free of organ support were not different for patients receiving ascorbate compared with those receiving placebo: mean (SD), 20.5 (9.5) days vs 19.0 (10.8) days, respectively (P = .528). The 90-day all-cause mortality was 15% in the ascorbate group vs 33% in the placebo group (P = .057). This was 1 of 19 secondary end points. Soluble tumor necrosis factor receptor 1 levels were reduced in the ascorbate group vs placebo from baseline to both day 2 (median, –861 pg/mL [interquartile range (IQR), –3,043 to 128.9 pg/mL] vs 241.4 pg/mL [–820 to 1,671 pg/mL]; P = .005) and day 3 (median, –1,511 pg/mL [IQR, –2,636 to –36.3 pg/mL] vs –131 pg/mL [–986 to 2,202 pg/mL]; P = .008).
Interpretation
Ascorbate did not improve days free of organ failure, although no safety concerns were identified in this small study. Ascorbate was shown to reduce a biological marker of inflammation associated with adverse outcomes in sepsis and lung injury.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
