Oral Vancomycin Is Not Associated With Meaningful Changes in Liver-Related End Points Among Adults With Primary Sclerosing Cholangitis: A Randomized, Placebo-Controlled Trial

INTRODUCTION: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease without approved medical therapies. We examined the efficacy and safety of oral vancomycin (OV) in those with PSC. METHODS: In this phase 3, 18-month, double-blind, placebo-controlled trial, we randomly assigned adults with PSC and a serum alkaline phosphatase (SAP) greater than 1.5 times the upper limit of normal to placebo or OV with dosages ranging from 125 to 375 mg 4 times daily pending biochemical response. The primary end point was normalization of SAP. RESULTS: Of the 82 patients who underwent randomization, 73 individuals had at least 1 outcome assessment. Individuals who withdrew early were less likely to rate their baseline health as excellent or very good (23.4% vs 54.5%, P < 0.01) despite having similar PSC prognostic features to those who completed the study. SAP normalization rates were similar (5% placebo, 6.7% OV, P = 1.00) after 18 months. Those who received OV had greater reduction in SAP (+1.2% placebo, -21.9% OV, P = 0.03). There were no differences in the changes in either the Mayo PSC risk score (-0.1 placebo, -0.1 OV, P = 0.88) or liver stiffness values (+0.1 kPa placebo, -4.0 kPa OV, P = 0.15). Discoloration of the teeth and tongue was the most common side effect of OV (17.5%). DISCUSSION: OV was not associated with clinically significant reductions in markers of PSC disease severity. Impairments in quality of life may influence patient retention in clinical trials.