Assessing the efficacy and safety of mycophenolate mofetil versus azathioprine in patients with autoimmune hepatitis (CAMARO trial): study protocol for a randomised controlled trial

Trials

Study Protocol

Amar D. Levens¹  Thomas Vanwolleghem²  Maartje Bartelink³  Sjoerd F. Bakker⁴  Adriaan J. van der Meer⁵  Martine A. M. C. Baven Pronk⁶  Ingrid A. M. Gisbertz⁷  Kerem Sebib Korkmaz⁸  Hendrik J. M. de Jonge⁹  Bart van Hoek^1,10  Anna E. C. Stoelinga^1,10  Maaike Biewenga^1,10  Maureen M. J. Guichelaar^1,11  Floris F. van den Brand^1,12  Joost P. H. Drenth^1,13  Romée J. A. L. M. Snijders^1,13  Simon Pape^1,13  Tom J. G. Gevers^1,14  Jan Maarten Vrolijk^1,15  Nicole M. F. van Gerven^1,16  Bart J. Verwer^1,17  Robert C. Verdonk^1,18  Marijn G. M. Sijtsma^1,19  Aad P. van den Berg^2,20  Khalida Soufidi^2,21  Ulrich H. W. Beuers^2,22  Ynto S. de Boer^2,23 

[1] Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands;Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium;Department of Gastroenterology and Hepatology, Deventer Hospital, Deventer, The Netherlands;Department of Gastroenterology and Hepatology, Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands;Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands;Department of Gastroenterology and Hepatology, Groene Hart Hospital, Gouda, The Netherlands;Department of Gastroenterology and Hepatology, Hospital Bernhoven, Uden, The Netherlands;Department of Gastroenterology and Hepatology, IJselland Hospital, Capelle aan den Ijssel, The Netherlands;Department of Gastroenterology and Hepatology, Jeroen Bosch Hospital, ‘s Hertogenbosch, The Netherlands;Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands;Department of Gastroenterology and Hepatology, Medisch Spectrum Twente, Enschede, The Netherlands;Department of Gastroenterology and Hepatology, OLVG Oost, Amsterdam, The Netherlands;Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands;European Reference Network RARE-LIVER, Hamburg, Germany;Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands;European Reference Network RARE-LIVER, Hamburg, Germany;Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands;Nutrim School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands;Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, The Netherlands;Department of Gastroenterology and Hepatology, Rode Kruis Hospital, Beverwijk, The Netherlands;Department of Gastroenterology and Hepatology, Spaarne Gasthuis, Haarlem, The Netherlands;Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, The Netherlands;Department of Gastroenterology and Hepatology, St. Jansdal Hospital, Harderwijk, The Netherlands;Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands;Department of Gastroenterology and Hepatology, Zuyderland, Heerlen, The Netherlands;European Reference Network RARE-LIVER, Hamburg, Germany;Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands;European Reference Network RARE-LIVER, Hamburg, Germany;Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, location VU University Medical Center, Amsterdam, The Netherlands;

关键词: Autoimmune hepatitis;    Azathioprine;    Mycophenolate mofetil;    First-line treatment;    Induction therapy;    Randomized controlled trial;    Remission;    Biochemical remission;    Phase IV trial;   

DOI  :  10.1186/s13063-022-06890-w

 received in 2022-06-01, accepted in 2022-11-05,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundCurrently, the standard therapy for autoimmune hepatitis (AIH) consists of a combination of prednisolone and azathioprine. However, 15% of patients are intolerant to azathioprine which necessitates cessation of azathioprine or changes in therapy. In addition, not all patients achieve complete biochemical response (CR). Uncontrolled data indicate that mycophenolate mofetil (MMF) can induce CR in a majority of patients. Better understanding of first-line treatment and robust evidence from randomised clinical trials are needed. The aim of this study was to explore the potential benefits of MMF as compared to azathioprine, both combined with prednisolone, as induction therapy in a randomised controlled trial in patients with treatment-naive AIH.MethodsCAMARO is a randomised (1:1), open-label, parallel-group, multicentre superiority trial. All patients with AIH are screened for eligibility. Seventy adult patients with AIH from fourteen centres in the Netherlands and Belgium will be randomised to receive MMF or azathioprine. Both treatment arms will start with prednisolone as induction therapy. The primary outcome is biochemical remission, defined as serum levels of alanine aminotransferase and immunoglobulin G below the upper limit of normal. Secondary outcomes include safety and tolerability of MMF and azathioprine, time to remission, changes in Model For End-Stage Liver Disease (MELD)-score, adverse events, and aspects of quality of life. The study period will last for 24 weeks.DiscussionThe CAMARO trial investigates whether treatment with MMF and prednisolone increases the proportion of patients in remission compared with azathioprine and prednisolone as the current standard treatment strategy. In addition, we reflect on the challenges of conducting a randomized trial in rare diseases.Trial registrationEudraCT 2016-001038-91. Prospectively registered on 18 April 2016.Graphical Abstract

【 授权许可】

CC BY   
© The Author(s) 2022

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