Fibrates for Itch (FITCH) in Fibrosing Cholangiopathies: A Double-Blind, Randomized, Placebo-Controlled Trial
| Autor: | Karin C M J van Nieuwkerk, Elsemieke de Vries, Nahid Mostafavi, Karel J. van Erpecum, Frans van der Heide, Ruth Bolier, Marleen de Vree, Albert Parés, Jorn C Goet, Jef Verbeek, Ulrich Beuers, Ronald P.J. Oude Elferink, Jeltje Helder, Cyriel Y. Ponsioen, Joost P.H. Drenth, Henk R. van Buuren |
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| Přispěvatelé: | Gastroenterology & Hepatology, VU University medical center, Amsterdam Gastroenterology Endocrinology Metabolism, MUMC+: MA Maag Darm Lever (9), RS: FHML non-thematic output, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Tytgat Institute for Liver and Intestinal Research |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Visual Analog Scale Primary Sclerosing Cholangitis (PSC) Placebo-controlled study Severity of Illness Index Gastroenterology Placebos 0302 clinical medicine Clinical endpoint skin and connective tissue diseases Cholestasis integumentary system Liver Cirrhosis Biliary primary sclerosing cholangitis (PSC) Middle Aged Ursodeoxycholic acid Treatment Outcome Female 030211 gastroenterology & hepatology primary biliary cholangitis (PBC) medicine.drug Adult medicine.medical_specialty Visual analogue scale Cholangitis Sclerosing Placebo digestive system Primary sclerosing cholangitis 03 medical and health sciences Primary Biliary Cholangitis (PBC) All institutes and research themes of the Radboud University Medical Center Double-Blind Method Internal medicine medicine Humans Bezafibrate Hepatology business.industry Pruritus pruritus medicine.disease digestive system diseases Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] 030104 developmental biology Quality of Life Secondary sclerosing cholangitis cholestasis business |
| Zdroj: | Gastroenterology, 160, 3, pp. 734-743.e6 Gastroenterology, 160(3), 734-743.e6. W.B. Saunders Gastroenterology, 160(3), 734-743.e6. W.B. Saunders Ltd Gastroenterology, 160(3), 734-743.e6. W B SAUNDERS CO-ELSEVIER INC Gastroenterology, 160(3), 734-+. Elsevier Saunders Netherlands Association for the Study of the Liver-Cholestasis Working Group 2021, ' Fibrates for Itch (FITCH) in Fibrosing Cholangiopathies: A Double-Blind, Randomized, Placebo-Controlled Trial ', Gastroenterology, vol. 160, no. 3, pp. 734-743.e6 . https://doi.org/10.1053/j.gastro.2020.10.001 Gastroenterology, 160, 734-743.e6 |
| ISSN: | 0016-5085 |
| DOI: | 10.1053/j.gastro.2020.10.001 |
| Popis: | BACKGROUND AND AIMS: Pruritus may seriously impair quality of life in patients with cholestatic diseases such as primary or secondary sclerosing cholangitis (PSC, SSC) and primary biliary cholangitis (PBC). Pharmacologic strategies show limited efficacy and can provoke serious side effects. We hypothesized that bezafibrate, a broad peroxisome proliferator-activated receptor (PPAR) agonist, relieves cholestasis-associated itch by alleviating hepatobiliary injury. The aim of this investigator-initiated FITCH trial (Fibrates for cholestatic ITCH) was to assess effects of bezafibrate on pruritus in patients with PSC, PBC, and SSC. METHODS: Patients with moderate to severe pruritus (≥5 of 10 on visual analog scale [VAS]) due to PSC, PBC, or SSC were recruited for this double-blind, randomized, placebo-controlled trial between 2016 and 2019. Patients received once-daily bezafibrate (400 mg) or placebo for 21 days. The primary end point was ≥50% reduction of pruritus (VAS; intention-to-treat). RESULTS: Of 74 randomized patients, 70 completed the trial (95%; 44 PSC, 24 PBC, 2 SSC). For the primary end point, bezafibrate led in 45% (41% PSC, 55% PBC) and placebo in 11% to ≥50% reduction of severe or moderate pruritus (P = .003). For secondary end points, bezafibrate reduced morning (P = .01 vs placebo) and evening (P = .007) intensity of pruritus (VAS) and improved the validated 5D-Itch questionnaire (P = .002 vs placebo). Bezafibrate also reduced serum alkaline phosphatase (-35%, P = .03 vs placebo) correlating with improved pruritus (VAS, P = .01) suggesting reduced biliary damage. Serum bile acids and autotaxin activity remained unchanged. Serum creatinine levels tended to mildly increase (3% bezafibrate, 5% placebo, P = .14). CONCLUSIONS: Bezafibrate is superior to placebo in improving moderate to severe pruritus in patients with PSC and PBC. TRIAL REGISTRATION: Netherlands Trial Register, ID: NTR5436 (August 3, 2015), ClinicalTrials.gov ID: NCT02701166 (March 2, 2016). ispartof: GASTROENTEROLOGY vol:160 issue:3 pages:734-+ ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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