Randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis

Gut. 2007 Oct;56(10):1439-44. doi: 10.1136/gut.2006.115873. Epub 2007 Mar 13.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • APACHE
  • Acetylcysteine / adverse effects
  • Acetylcysteine / blood
  • Acetylcysteine / therapeutic use
  • Acute Disease
  • Adult
  • Aged
  • Antioxidants / adverse effects
  • Antioxidants / pharmacokinetics
  • Antioxidants / therapeutic use*
  • Ascorbic Acid / adverse effects
  • Ascorbic Acid / blood
  • Ascorbic Acid / therapeutic use
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects
  • Pancreatitis / blood
  • Pancreatitis / drug therapy*
  • Selenium / adverse effects
  • Selenium / blood
  • Selenium / therapeutic use
  • Treatment Outcome

Substances

  • Antioxidants
  • Selenium
  • Ascorbic Acid
  • Acetylcysteine