Abstract
BackgroundPruritus (itch) is a frequent, burdensome and difficult-to-treat symptom in patients with cholestasis. Fibrates are currently under investigation for the treatment of primary biliary cholangitis in patients with a suboptimal response to ursodeoxycholic acid. Moreover, there is empirical evidence for a possible antipruritic effect. We aim to prove this in a randomized controlled trial, including patients with cholestatic liver diseases other than primary biliary cholangitis that are accompanied by pruritus.MethodsA multicenter investigator-initiated, double-blind, randomized placebo-controlled trial to evaluate the effect of bezafibrate on cholestatic pruritus in 84 adult patients with primary biliary cholangitis or primary/secondary sclerosing cholangitis. Primary outcome is the proportion of patients with a reduction of itch intensity of 50% or more (measured on a Visual Analog Scale) after 21 days of treatment with bezafibrate 400 mg qid or placebo. Secondary outcomes include the effect of bezafibrate on a five-dimensional itch score, liver disease-specific quality of life, serum liver tests and autotaxin activity. Safety will be evaluated through serum parameters for kidney function and rhabdomyolysis as well as precise recording of (serious) adverse events. We provide a schematic overview of the study protocol and describe the methods used to recruit and randomize patients, collect and handle data and perform statistical analyses.DiscussionGiven its favorable safety profile and anticholestatic properties, bezafibrate may become the new first-line treatment option for treating cholestatic pruritus.Trial registrationNetherlands Trial Register, ID: NCT02701166. Registered on 2 March 2016;Netherlands Trial Register, ID: NTR5436. Registered on 3 August 2015.
Highlights
Pruritus is a frequent, burdensome and difficult-to-treat symptom in patients with cholestasis
A wide variety of cholestatic conditions are associated with pruritus, including primary biliary cholangitis (PBC, formerly referred to as primary biliary cirrhosis [1]) and primary sclerosing cholangitis (PSC)
Topical menthol-containing agents are allowed, as well as bile salt sequestrants as long as they are taken at least 4 h before or after intake of the study medication. Incidental use of these agents should be noted by patients in the diary, structural use should be noted on the Case Report Form (CRF) Pregnancy, women of childbearing potential not using contraception, breastfeeding Cholestasis due to obstruction that requires invasive desobstructive treatment within the time scope of the study (5 weeks) such as endoscopic retrograde cholangiopancreaticography (ERCP) or surgical removal of a tumor compressing the bile duct Use of opiates Renal insufficiency N.B
Summary
Pruritus (itch) is a frequent, burdensome and difficult-to-treat symptom in patients with cholestasis. Fibrates are currently under investigation for the treatment of primary biliary cholangitis in patients with a suboptimal response to ursodeoxycholic acid. We aim to prove this in a randomized controlled trial, including patients with cholestatic liver diseases other than primary biliary cholangitis that are accompanied by pruritus. A wide variety of cholestatic conditions are associated with pruritus (itch), including primary biliary cholangitis (PBC, formerly referred to as primary biliary cirrhosis [1]) and primary sclerosing cholangitis (PSC). The pruritus can occur locally or be generalized and is often reported by patients as the most burdensome symptom of their disease. Liver transplantation turns out to be the only option left [3]
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