title: Randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis.
abstract: BACKGROUND
  Based on equivocal clinical data, intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis. To date there is no randomised comparison of this therapy in severe acute pancreatitis.
  
  
  METHODS
  We conducted a randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in patients with predicted severe acute pancreatitis. Forty-three patients were enrolled from three hospitals in the Manchester (UK) area over the period June 2001 to November 2004. Randomisation stratified for APACHE-II score and hospital site, and delivered groups that were similar at baseline.
  
  
  RESULTS
  Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial. However, at 7 days, there was no statistically significant difference in the primary end point, organ dysfunction (antioxidant vs placebo: 32% vs 17%, p = 0.33) or any secondary end point of organ dysfunction or patient outcome.
  
  
  CONCLUSIONS
  This study provides no evidence to justify continued use of n-acetylcysteine, selenium, vitamin C based antioxidant therapy in severe acute pancreatitis. In the context of any future trial design, careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study.
authors.affiliation: Hepatobiliary Unit, Department of Surgery, Manchester Royal Infirmary, Manchester M13 9WL, UK. ajith.siriwardena@cmmc.nhs.uk
authors.forename: Ajith K
authors.initials: AK
authors.lastname: Siriwardena
authors.forename: James M
authors.initials: JM
authors.lastname: Mason
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Balachandra
authors.forename: Anil
authors.initials: A
authors.lastname: Bagul
authors.forename: Simon
authors.initials: S
authors.lastname: Galloway
authors.forename: Laura
authors.initials: L
authors.lastname: Formela
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Hardman
authors.forename: Saurabh
authors.initials: S
authors.lastname: Jamdar
mesh_terms: D018806:APACHE; D000111:Acetylcysteine / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D000208:Acute Disease; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D010195:Pancreatitis / Q000097:blood / Q000188:drug therapy*; D012643:Selenium / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D012643:Selenium; D001205:Ascorbic Acid; D000111:Acetylcysteine