Tacrolimus versus mycophenolate for AutoImmune hepatitis patients with incompLete response On first-line therapy (TAILOR study): a study protocol for a phase III, open-label, multicentre, randomised controlled trial.

Autor: Stoelinga AEC; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands. a.e.c.stoelinga@lumc.nl., Tushuizen ME; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands., van den Hout WB; Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands., Girondo MDMR; Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands., de Vries ES; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.; Department of Gastroenterology and Hepatology, Isala Hospital, Zwolle, The Netherlands., Levens AD; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands., Moes DAR; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands., Gevers TJG; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.; European Reference Network RARE-LIVER, Hamburg, Germany., van der Meer S; Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands., Brouwer HT; Department of Gastroenterology and Hepatology, Reinier de Graaf Gasthuis, Delft, The Netherlands., de Jonge HJM; Department of Gastroenterology and Hepatology, Jeroen Bosch Hospital, 'S-Hertogenbosch, The Netherlands., de Boer YS; European Reference Network RARE-LIVER, Hamburg, Germany.; Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Location VU University Medical Center, Amsterdam, The Netherlands., Beuers UHW; European Reference Network RARE-LIVER, Hamburg, Germany.; Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Location Academic Medical Center, Amsterdam, The Netherlands., van der Meer AJ; European Reference Network RARE-LIVER, Hamburg, Germany.; Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands., van den Berg AP; European Reference Network RARE-LIVER, Hamburg, Germany.; Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands., Guichelaar MMJ; Department of Gastroenterology and Hepatology, Medisch Spectrum Twente, Enschede, The Netherlands., Drenth JPH; European Reference Network RARE-LIVER, Hamburg, Germany.; Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands., van Hoek B; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
Jazyk: angličtina
Zdroj: Trials [Trials] 2024 Jan 17; Vol. 25 (1), pp. 61. Date of Electronic Publication: 2024 Jan 17.
DOI: 10.1186/s13063-023-07832-w
Abstrakt: Background: Autoimmune hepatitis (AIH) is a rare, chronic inflammatory disease of the liver. The treatment goal is reaching complete biochemical response (CR), defined as the normalisation of aspartate and alanine aminotransferases and immunoglobulin gamma. Ongoing AIH activity can lead to fibrosis and (decompensated) cirrhosis. Incomplete biochemical response is the most important risk factor for liver transplantation or liver-related mortality. First-line treatment consists of a combination of azathioprine and prednisolone. If CR is not reached, tacrolimus (TAC) or mycophenolate mofetil (MMF) can be used as second-line therapy. Both products are registered for the prevention of graft rejection in solid organ transplant recipients. The aim of this study is to compare the effectiveness and safety of TAC and MMF as second-line treatment for AIH.
Methods: The TAILOR study is a phase IIIB, multicentre, open-label, parallel-group, randomised (1:1) controlled trial performed in large teaching and university hospitals in the Netherlands. We will enrol 86 patients with AIH who have not reached CR after at least 6 months of treatment with first-line therapy. Patients are randomised to TAC (0.07 mg/kg/day initially and adjusted by trough levels) or MMF (max 2000 mg/day), stratified by the presence of cirrhosis at inclusion. The primary endpoint is the difference in the proportion of patients reaching CR after 12 months. Secondary endpoints include the difference in the proportion of patients reaching CR after 6 months, adverse effects, difference in fibrogenesis, quality of life and cost-effectiveness.
Discussion: This is the first randomised controlled trial comparing two second-line therapies for AIH. Currently, second-line treatment is based on retrospective cohort studies. The rarity of AIH is the main issue in clinical research for alternative treatment options. The results of this trial can be implemented in existing international clinical guidelines.
Trial Registration: ClinicalTrials.gov NCT05221411 . Retrospectively registered on 3 February 2022; EudraCT number 2021-003420-33. Prospectively registered on 16 June 2021.
(© 2024. The Author(s).)
Databáze: MEDLINE
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