Open-label prospective therapeutic clinical trials: oral vancomycin in children and adults with primary sclerosing cholangitis. (2nd August 2020)

• Record Type: Journal Article
• Authors: Ali, Ahmad Hassan; Damman, Jennifer; Shah, Shamita B.; Davies, Yinka; Hurwitz, Melissa; Stephen, Mariam; Lemos, Leta M.; Carey, Elizabeth J.; Lindor, Keith D.; Buness, Cynthia W.; Alrabadi, Leina; Berquist, William E.; Cox, Kenneth L.
• Is Part Of: Scandinavian journal of gastroenterology. Volume 55:Number 8(2020)
• Page Start: 941
• Page End: 950
• Publication Date: 2020-08-02
• Subjects: Primary sclerosing cholangitis -- cirrhosis -- liver biochemistry -- cholangiography -- inflammatory bowel disease -- and ulcerative colitis; Gastroenterology -- Periodicals; Digestive organs -- Diseases -- Periodicals; 616.33
• DOI: 10.1080/00365521.2020.1787501
• Languages: English
• ISSNs: 0036-5521

Abstract

Abstract: Background: Oral vancomycin (OV) in primary sclerosing cholangitis (PSC) has been evaluated as a potential therapeutic agent. We report the long-term biochemical course and outcomes of patients with PSC treated with OV. Methods: Patients were enrolled in 2 open-label clinical trials (ClinicalTrials.gov Identifier: NCT01802073 and NCT01322386) and offered OV at 50 mg/kg/day in 3 divided doses if weight <30kg, and 500 mg 3 times/day if weight ≥30kg. Patients with biliary strictures requiring stenting or awaiting liver transplant were excluded. Liver biochemistry, MRCP and histology were documented at baseline and while on OV. The primary outcome was a decrease in elevated gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), and/or alanine aminotransferase (ALT) from baseline. Results: 30 subjects were enrolled, and 29 additional subjects who learned of the clinical trial requested OV (total n = 59; median age was 13.5 years [range, 1.5–44 years]; 64.4% were male; and 94.9% had inflammatory bowel disease [IBD]). The median treatment duration was 2.7 years (range, 0.2–14 years). Ninety-six percent (57/59), 81.3% (48/59), and 94.9% (56/59) experienced reduction of GGT, ALP, and ALT, respectively. Furthermore, 39% (23/59), 22% (13/59), and 55.9% (33/59) experienced normalization of GGT, ALP, and ALT, respectively, within the first 6 months of OV treatment. One patient underwent liver transplantation 8 years after beginning OV treatment, and one developed biliary strictures requiring endoscopic intervention. OV was well-tolerated by patients, and no patient developed treatment-related adverse events. Conclusion: In PSC, OV was well-tolerated and was associated with improvement in liver chemistry. A randomized placebo-controlled clinical trial is warranted.