Assessing the efficacy and safety of mycophenolate mofetil versus azathioprine in patients with autoimmune hepatitis (CAMARO trial): study protocol for a randomised controlled trial
Abstract Background Currently, 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 ach...
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Trials |
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| Online Access: | https://doi.org/10.1186/s13063-022-06890-w |
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| author | Romée J. A. L. M. Snijders Anna E. C. Stoelinga Tom J. G. Gevers Simon Pape Maaike Biewenga Robert C. Verdonk Hendrik J. M. de Jonge Jan Maarten Vrolijk Sjoerd F. Bakker Thomas Vanwolleghem Ynto S. de Boer Martine A. M. C. Baven Pronk Ulrich H. W. Beuers Adriaan J. van der Meer Nicole M. F. van Gerven Marijn G. M. Sijtsma Bart J. Verwer Ingrid A. M. Gisbertz Maartje Bartelink Floris F. van den Brand Kerem Sebib Korkmaz Aad P. van den Berg Maureen M. J. Guichelaar Khalida Soufidi Amar D. Levens Bart van Hoek Joost P. H. Drenth on behalf of the Dutch Autoimmune Hepatitis Working Group |
| author_facet | Romée J. A. L. M. Snijders Anna E. C. Stoelinga Tom J. G. Gevers Simon Pape Maaike Biewenga Robert C. Verdonk Hendrik J. M. de Jonge Jan Maarten Vrolijk Sjoerd F. Bakker Thomas Vanwolleghem Ynto S. de Boer Martine A. M. C. Baven Pronk Ulrich H. W. Beuers Adriaan J. van der Meer Nicole M. F. van Gerven Marijn G. M. Sijtsma Bart J. Verwer Ingrid A. M. Gisbertz Maartje Bartelink Floris F. van den Brand Kerem Sebib Korkmaz Aad P. van den Berg Maureen M. J. Guichelaar Khalida Soufidi Amar D. Levens Bart van Hoek Joost P. H. Drenth on behalf of the Dutch Autoimmune Hepatitis Working Group |
| author_sort | Romée J. A. L. M. Snijders |
| collection | DOAJ |
| description | Abstract Background Currently, 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. Methods CAMARO 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. Discussion The 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 registration EudraCT 2016-001038-91 . Prospectively registered on 18 April 2016. Graphical Abstract |
| first_indexed | 2024-04-13T04:38:01Z |
| format | Article |
| id | doaj.art-94c4694744e64d888bdd6fba2110a79f |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-04-13T04:38:01Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-94c4694744e64d888bdd6fba2110a79f2022-12-22T03:02:07ZengBMCTrials1745-62152022-12-0123111310.1186/s13063-022-06890-wAssessing the efficacy and safety of mycophenolate mofetil versus azathioprine in patients with autoimmune hepatitis (CAMARO trial): study protocol for a randomised controlled trialRomée J. A. L. M. Snijders0Anna E. C. Stoelinga1Tom J. G. Gevers2Simon Pape3Maaike Biewenga4Robert C. Verdonk5Hendrik J. M. de Jonge6Jan Maarten Vrolijk7Sjoerd F. Bakker8Thomas Vanwolleghem9Ynto S. de Boer10Martine A. M. C. Baven Pronk11Ulrich H. W. Beuers12Adriaan J. van der Meer13Nicole M. F. van Gerven14Marijn G. M. Sijtsma15Bart J. Verwer16Ingrid A. M. Gisbertz17Maartje Bartelink18Floris F. van den Brand19Kerem Sebib Korkmaz20Aad P. van den Berg21Maureen M. J. Guichelaar22Khalida Soufidi23Amar D. Levens24Bart van Hoek25Joost P. H. Drenth26on behalf of the Dutch Autoimmune Hepatitis Working GroupDepartment of Gastroenterology and Hepatology, Radboud University Medical CenterDepartment of Gastroenterology and Hepatology, Leiden University Medical CenterDepartment of Gastroenterology and Hepatology, Radboud University Medical CenterDepartment of Gastroenterology and Hepatology, Radboud University Medical CenterDepartment of Gastroenterology and Hepatology, Leiden University Medical CenterDepartment of Gastroenterology and Hepatology, St. Antonius HospitalDepartment of Gastroenterology and Hepatology, Jeroen Bosch HospitalDepartment of Gastroenterology and Hepatology, Rijnstate HospitalDepartment of Gastroenterology and Hepatology, Elisabeth-Tweesteden HospitalDepartment of Gastroenterology and Hepatology, Antwerp University HospitalEuropean Reference Network RARE-LIVERDepartment of Gastroenterology and Hepatology, Groene Hart HospitalEuropean Reference Network RARE-LIVERDepartment of Gastroenterology and Hepatology, Erasmus University Medical CenterDepartment of Gastroenterology and Hepatology, Rode Kruis HospitalDepartment of Gastroenterology and Hepatology, St. Jansdal HospitalDepartment of Gastroenterology and Hepatology, Spaarne GasthuisDepartment of Gastroenterology and Hepatology, Hospital BernhovenDepartment of Gastroenterology and Hepatology, Deventer HospitalDepartment of Gastroenterology and Hepatology, OLVG OostDepartment of Gastroenterology and Hepatology, IJselland HospitalDepartment of Gastroenterology and Hepatology, University Medical Center GroningenDepartment of Gastroenterology and Hepatology, Medisch Spectrum TwenteDepartment of Gastroenterology and Hepatology, ZuyderlandDepartment of Clinical Pharmacy and Toxicology, Leiden University Medical CenterDepartment of Gastroenterology and Hepatology, Leiden University Medical CenterDepartment of Gastroenterology and Hepatology, Radboud University Medical CenterAbstract Background Currently, 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. Methods CAMARO 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. Discussion The 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 registration EudraCT 2016-001038-91 . Prospectively registered on 18 April 2016. Graphical Abstracthttps://doi.org/10.1186/s13063-022-06890-wAutoimmune hepatitisAzathioprineMycophenolate mofetilFirst-line treatmentInduction therapyRandomized controlled trial |
| spellingShingle | Romée J. A. L. M. Snijders Anna E. C. Stoelinga Tom J. G. Gevers Simon Pape Maaike Biewenga Robert C. Verdonk Hendrik J. M. de Jonge Jan Maarten Vrolijk Sjoerd F. Bakker Thomas Vanwolleghem Ynto S. de Boer Martine A. M. C. Baven Pronk Ulrich H. W. Beuers Adriaan J. van der Meer Nicole M. F. van Gerven Marijn G. M. Sijtsma Bart J. Verwer Ingrid A. M. Gisbertz Maartje Bartelink Floris F. van den Brand Kerem Sebib Korkmaz Aad P. van den Berg Maureen M. J. Guichelaar Khalida Soufidi Amar D. Levens Bart van Hoek Joost P. H. Drenth on behalf of the Dutch Autoimmune Hepatitis Working Group 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 Autoimmune hepatitis Azathioprine Mycophenolate mofetil First-line treatment Induction therapy Randomized controlled trial |
| title | Assessing the efficacy and safety of mycophenolate mofetil versus azathioprine in patients with autoimmune hepatitis (CAMARO trial): study protocol for a randomised controlled trial |
| title_full | Assessing the efficacy and safety of mycophenolate mofetil versus azathioprine in patients with autoimmune hepatitis (CAMARO trial): study protocol for a randomised controlled trial |
| title_fullStr | Assessing the efficacy and safety of mycophenolate mofetil versus azathioprine in patients with autoimmune hepatitis (CAMARO trial): study protocol for a randomised controlled trial |
| title_full_unstemmed | Assessing the efficacy and safety of mycophenolate mofetil versus azathioprine in patients with autoimmune hepatitis (CAMARO trial): study protocol for a randomised controlled trial |
| title_short | Assessing the efficacy and safety of mycophenolate mofetil versus azathioprine in patients with autoimmune hepatitis (CAMARO trial): study protocol for a randomised controlled trial |
| title_sort | assessing the efficacy and safety of mycophenolate mofetil versus azathioprine in patients with autoimmune hepatitis camaro trial study protocol for a randomised controlled trial |
| topic | Autoimmune hepatitis Azathioprine Mycophenolate mofetil First-line treatment Induction therapy Randomized controlled trial |
| url | https://doi.org/10.1186/s13063-022-06890-w |
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