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

Aliment Pharmacol Ther. 2013 Mar;37(6):604-12. doi: 10.1111/apt.12232. Epub 2013 Feb 5.

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).

Publication types

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

MeSH terms

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

Substances

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

Associated data

  • ClinicalTrials.gov/NCT01085760