Randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis.
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.
Siriwardena
Ajith K
AK
Hepatobiliary Unit, Department of Surgery, Manchester Royal Infirmary, Manchester M13 9WL, UK. ajith.siriwardena@cmmc.nhs.uk
Mason
James M
JM
Balachandra
Srinivasan
S
Bagul
Anil
A
Galloway
Simon
S
Formela
Laura
L
Hardman
Jonathan G
JG
Jamdar
Saurabh
S
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
D000975:Antioxidants; D012643:Selenium; D001205:Ascorbic Acid; D000111:Acetylcysteine