Efficacy and Security of Bezafibrate in Patients With Primary Biliary Cirrhosis Without Biochemical Response to Ursodeoxycholic Acid: A Randomized, Double-blind, Placebo-controlled Trial

There are case reports and pilot studies in patients with primary biliary cholangitis (PBC) In the literature in which the effect of fibrates (specially bezafibrate) on the improvement of biochemical cholestasis have been seen, however the clinical benefit (survival, mortality, fatigue, pruritus) has not been reported and likewise the response criteria used in previous studies is very heterogeneous. In previous studies, bezafibrate has been proved to be a secure drug in this patients, with few adverse events, also it is an economic and of easy access drug. For all this the investigators intent to study the utility of bezafibrate as an additional treatment in PBC patients without response to UDCA.

This is a randomized, placebo-controlled, parallel-group study designed to enroll a total of 34 patients with diagnosis of PBC without a complete response to the use of UDCA for more than a year, then the participants will be divided by randomization to receive bezafibrate or placebo, resulting in a total of two groups of 17 patients each. Both groups will be followed every 3 months for a total of 1 year with clinical and laboratory follow-up to determine the efficacy and security of the treatment. The investigators will measure all the laboratory variables related to the disease and possible adverse effects of the use of fibrates (creatine kinase, transaminases, bilirubin, alkaline phosphatase), also the investigators will measure the quality of life variables (pruritus severity, Short Form [SF]-36 questionnaire), and determine the fibrosis stage at the beginning and end of the study by non-invasive methods (transient elastography).

The study is directed to patients with PBC diagnosis who have had management with standard UDCA dose (13 to 15 mg/kg per day) for at least 6 months and had not reached complete biochemical response, defined by Paris II criteria. The dose of fibrate to use will be bezafibrate 200 mg every 12 hours or placebo every 12 hours for 12 months, both having the exact characteristics to avoid their recognition. Patients will continue the administration of UDCA at the same dose at enrollment. The intervention will be for a period of 12 months, with a follow-up every 3 months completing 5 medical follow-up visits (0, 3, 6, 9 and 12 months).