Randomized, double-blind, placebo-controlled trial of Intravenous (n-acetylcysteine, selenium, vitamin c) Antioxidant therapy in severe acute pancreatitis

Ajith K Siriwardena ^1*, James M Mason ², Srinivasan Balachandra ¹, Anil Bagul ¹, Simon Galloway Mr³, Laura Formela ⁴, Jonathan G Hardman ¹ and Saurabh Jamdar ¹

¹ Hepatobiliary Unit, Manchester Royal Infirmary, United Kingdom
² School for Health, University of Durham, United Kingdom
³ Department of Upper GI Surgery, Wythenshawe Hospital, United Kingdom
⁴ Department of Upper GI Surgery, Hope Hospital, Salford, United Kingdom

^* To whom correspondence should be addressed. E-mail: ajith.siriwardena{at}cmmc.nhs.uk.

Accepted 26 February 2007

Abstract

Background: Based on equivocal clinical data, intravenous anti-oxidant therapy has been used for the treatment of severe acute pancreatitis. To date there is no randomized comparison of this therapy in severe acute pancreatitis.

Methods: We conducted a randomized, double-blind, placebo controlled trial of intravenous (n- acetylcysteine, selenium, vitamin c) anti-oxidant 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 endpoint, organ dysfunction (Antioxidant vs. Placebo: 32% vs. 17%, p=0.33) or any secondary endpoint of organ dysfunction or patient outcome.

Conclusions: This study provides no evidence to justify continued use of selenium, n-acetylcysteine, 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 toward adverse outcome in patients in the treatment arm of this study.

Keywords: acute pancreatitis, randomized controlled trial, anti-oxidant

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