Randomised clinical trial: vancomycin or metronidazole in patients with primary sclerosing cholangitis - a pilot study.

Abstract

BACKGROUND:

Emerging data suggest that oral antibiotics may have therapeutic effects in primary sclerosing cholangitis (PSC), but published studies are limited.

AIMS:

To investigate the safety and efficacy of oral vancomycin and metronidazole in patients with PSC.

METHODS:

Thirty-five patients with PSC were randomised in a double-blind manner into four groups: vancomycin 125 mg or 250 mg four times/day, or metronidazole 250 mg or 500 mg three times/day for 12 weeks. The primary endpoint was decrease in alkaline phosphatase (ALK) at 12 weeks. Secondary end points included serum bilirubin and Mayo PSC risk score; pruritus; and adverse effects (AEs). Nonparametric tests were used for analysis.

RESULTS:

The primary endpoint was reached in the low-dose (-43% change in ALK, P = 0.03) and high-dose (-40%, P = 0.02) vancomycin groups, with two patients in the former experiencing ALK normalisation. Bilirubin decreased significantly in the low-dose metronidazole group (-20%, P = 0.03) and trended towards significance in the low-dose vancomycin group (-33%, P = 0.06). Mayo PSC risk score decreased significantly in the low-dose vancomycin (-0.55, P = 0.02) and low-dose metronidazole group (-0.16, P = 0.03). Pruritus decreased significantly in the high-dose metronidazole group (-3.4, P = 0.03). AEs led to medication discontinuation in six patients, four of whom were receiving metronidazole.

CONCLUSIONS:

Both vancomycin and metronidazole demonstrated efficacy; however, only patients in the vancomycin groups reached the primary endpoint, and with less adverse effects. Larger, longer-term studies are needed to further examine the safety and efficacy of antibiotics as a potential treatment for patients with primary sclerosing cholangitis (clinicaltrials.gov NCT01085760).

• Authors: J H Tabibian, E Weeding, R A Jorgensen, J L Petz, J C Keach, J A Talwalkar, K D Lindor
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 37 Issue 6 Pg. 604-12 (Mar 2013) ISSN: 1365-2036 [Electronic] England
• PMID: 23384404 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Blackwell Publishing Ltd.

Chemical References

• Anti-Bacterial Agents
• Biomarkers
• Metronidazole
• Vancomycin
• Bilirubin

Topics

• Adult
• Aged
• Anti-Bacterial Agents (adverse effects, therapeutic use)
• Bilirubin
• Biomarkers
• Cholangitis, Sclerosing (drug therapy)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Male
• Metronidazole (adverse effects, therapeutic use)
• Middle Aged
• Pilot Projects
• Vancomycin (adverse effects, therapeutic use)
• Young Adult