TY - JOUR
T1 - Fibrates for the treatment of cholestatic itch (FITCH)
T2 - Study protocol for a randomized controlled trial
AU - Bolier, Ruth
AU - de Vries, Elsemieke S.
AU - Parés, Albert
AU - Helder, Jeltje
AU - Kemper, E. Marleen
AU - Zwinderman, Koos
AU - Elferink, Ronald P.Oude
AU - Beuers, Ulrich
AU - van Buuren, Henk R.
AU - Drenth, Joost P.
AU - van Erpecum, Nijmegen Karel J.
AU - van Hoek, Bart
AU - Jansen, Peter L.M.
AU - van Nieuwkerk, Karin M.
AU - de Vree, J. Marleen
AU - Netherlands Association for the Study of the Liver (NASL) Cholestatic Liver Diseases Study Group
N1 - Funding Information:
This study is financed by the Dutch Society of Gastroenterology (NVGE, external, grant 2015-09), Dr. Falk Pharma Benelux (external, grant NL-2015-017-R2) and the Academic Medical Center Foundation (internal, grant 2016/0101), awarded to UB and grant PI15/797 from the Instituto de Salud Carlos III (external), partially supported by the European Regional Development Fund, to AP. The funding parties were not involved in the design of the study and will neither be involved in data collection, analysis and/or interpretation, nor in writing or reviewing the manuscript. The primary sponsor of this trial is Prof. Dr. UH Beuers, Academic Medical Center, Amsterdam, The Netherlands, who is not the main funder but is responsible for initiating, managing, registering and obtaining financial resources for this study. The secondary sponsor is Prof. Dr. A Parés, Hospital Clínic, Barcelona, Spain, who takes responsibility for managing and obtaining financial resources for the study in Barcelona.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/5/23
Y1 - 2017/5/23
N2 - Background: 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. 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. Methods: A 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. Discussion: Given its favorable safety profile and anticholestatic properties, bezafibrate may become the new first-line treatment option for treating cholestatic pruritus. Trial registration: Netherlands Trial Register, ID: NCT02701166. Registered on 2 March 2016; Netherlands Trial Register, ID: NTR5436. Registered on 3 August 2015.
AB - Background: 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. 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. Methods: A 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. Discussion: Given its favorable safety profile and anticholestatic properties, bezafibrate may become the new first-line treatment option for treating cholestatic pruritus. Trial registration: Netherlands Trial Register, ID: NCT02701166. Registered on 2 March 2016; Netherlands Trial Register, ID: NTR5436. Registered on 3 August 2015.
KW - Bezafibrate
KW - Itch
KW - Primary biliary cholangitis
KW - Primary sclerosing cholangitis
KW - Pruritus
KW - Secondary sclerosing cholangitis
U2 - 10.1186/s13063-017-1966-8
DO - 10.1186/s13063-017-1966-8
M3 - Article
SN - 1745-6215
VL - 18
JO - Trials
JF - Trials
IS - 1
M1 - 230
ER -