Randomised clinical trial: vancomycin or metronidazole in patients with primary
sclerosing cholangitis - a pilot study.
Author(s): Tabibian JH(1), Weeding E, Jorgensen RA, Petz JL, Keach JC, Talwalkar JA, Lindor
KD.
Affiliation(s): Author information:
(1)Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
Publication date & source: 2013, Aliment Pharmacol Ther. , 37(6):604-12
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).
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