Administrative information
Title {1} | Tacrolimus versus mycophenolate for AutoImmune hepatitis patients with incompLete response On first line therapy: a Randomised trial (TAILOR study) |
Trial registration {2a and 2b}. | EudraCT 2021–003420-33 ClinicalTrials.gov Identifier: NCT05221411 EU-CT number: 2023-509491-42-00 |
Protocol version {3} | Version 2.9, 28-09-2021. |
Funding {4} | Grant from ZonMw, number: 10140022010001 And funding from Chiesi Pharmaceuticals b.v. (project number: PA 2019–71111/vjanssen) |
Author details {5a} | 1. Department of gastroenterology and hepatology, Leiden University Medical Center, Leiden, The Netherlands 2. Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands 3. Department of gastroenterology and hepatology, Isala Hospital, Zwolle, The Netherlands 4. Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands 5. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands 6. Department of gastroenterology and hepatology, University Medical Center Utrecht, The Netherlands 7. Department of gastroenterology and hepatology, Reinier de Graaf Gasthuis, The Netherlands 8. Department of Gastroenterology and Hepatology, Jeroen Bosch Hospital, ‘s Hertogenbosch, The Netherlands 9. Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, location VU University Medical Center, Amsterdam, The Netherlands 10. Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, location Academic Medical Center, Amsterdam, The Netherlands 11. Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands 12. Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands 13. Department of Gastroenterology and Hepatology, Medisch Spectrum Twente, Enschede, The Netherlands 14. Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands 15. Department of Gastroenterology and Hepatology, Elisabeth Tweesteden Hospital, Tilburg, the Netherlands 16. Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, the Netherlands 17. Department of Gastroenterology and Hepatology, Haaglanden Medical Center, The Hague, The Netherlands 18. Department of Gastroenterology and Hepatology, Rode Kruis Hospital, Beverwijk, the Netherlands 19. European Reference Network RARE-LIVER |
Name and contact information for the trial sponsor {5b} | Prof. dr. B. van Hoek Leiden University Medical Center Department of Gastroenterology and Hepatology, C4P P.O. Box 9600 2300 RC Leiden, the Netherlands b.v_hoek@lumc.nl Phone: 071–5291111/5299756/5263507 |
Role of sponsor {5c} | The funders have no role in the study design, collection, or management of data. Neither ZonMw nor Chiesi Pharmaceuticals b.v. have access to coded of decoded data. The funders do not play a role in the analysis or publication process of this study. |
Introduction
Background and rationale {6a}
Objectives {7}
Trial design {8}
Methods: participants, interventions and outcomes
Study setting {9}
Eligibility criteria {10}
Inclusion criteria
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Patient is older than 18 years old.
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Incomplete responder on at least a half year of first-line treatment, including azathioprine/6-MP/6-TG and prednisolone or budesonide.
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ALT 1.5–10 × ULN for at least 2 months.
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Patient is capable of understanding the purpose and risks of the study, has been fully informed and has given written informed consent to participate in the study.
Exclusion criteria
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Presence of decompensated liver disease, defined as ascites, coagulopathy (INR > 1.5), encephalopathy, variceal bleed, hepato-pulmonal syndrome, hepatorenal syndrome or HCC in the past 6 months
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Signs of other liver diseases as metabolic-dysfunction associated steatotic liver disease (MASLD), Wilson disease, hemochromatosis, alcoholic liver disease or viral hepatitis B/C/D
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Clinical diagnosis of overlap/variant syndrome with PBC or PSC
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Liver transplantation in the medical history or currently on the waiting list for liver transplantation
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Incompliance with therapy during the last 12 months
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Active infections during inclusion including latent tuberculosis and HIV co-infection
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Allergic or hypersensitive to TAC or MMF
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An estimated glomerular filtration rate (eGFR) of < 60 mL/min
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Pregnancy or intention to become pregnant in the next 12 months
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Use of TAC or MMF in the past
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Malignancy in the medical history in the past 5 years, or current use of chemotherapy.
Who will take informed consent? {26a}
Additional consent provisions for collection and use of participant data and biological specimens {26b}
Interventions
Explanation for the choice of comparators {6b}
Intervention description {11a}
Criteria for discontinuing or modifying allocated interventions {11b}
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A flare of AIH (ALT > 10xULN) occurs
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Other urgent medical reasons (e.g. pregnancy (for patients assigned to MMF) or acute (on chronic) liver failure)