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Randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis
  1. Ajith K Siriwardena1,
  2. James M Mason2,
  3. Srinivasan Balachandra1,
  4. Anil Bagul1,
  5. Simon Galloway3,
  6. Laura Formela4,
  7. Jonathan G Hardman1,
  8. Saurabh Jamdar2
  1. 1Hepatobiliary Surgery Unit, Department of Surgery, Manchester Royal Infirmary, Manchester, UK
  2. 2School for Health, University of Durham, UK
  3. 3Department of Upper GI Surgery, Wythenshawe Hospital, Manchester, UK
  4. 4Department of Upper GI Surgery, Hope Hospital, Salford, UK
  1. Correspondence to:
    Dr Ajith K Siriwardena
    Hepatobiliary Unit, Department of Surgery, Manchester Royal Infirmary, Manchester M13 9WL, UK; ajith.siriwardena{at}cmmc.nhs.uk

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.

  • CRFs, case report forms
  • ERC, endoscopic retrograde cholangiography
  • GSH, glutathione
  • GSSG, glutathione disulphide
  • HDU, high dependency unit
  • HO-1, haem oxygenase
  • IQR, interquartile range
  • ITU, intensive care unit
  • LODS, logistic organ dysfunction score
  • MODS, Marshall organ dysfunction score
  • MT-1, metallothionein
  • pancreatitis
  • antioxidants
  • randomised controlled trial
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Footnotes

  • Published Online First 3 March 2007

  • Financial support: This study was supported by a grant from the Pancreatitis Patients’ Support Group at Manchester Royal Infirmary and the costs of antioxidants and placebo were met by Pharmanord UK.

  • Conflicts of interest: none.

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