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

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. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Stoelinga, Anna E. C. [verfasserIn] Tushuizen, Maarten E. van den Hout, Wilbert B. Girondo, Mar D. M. Rodriguez de Vries, Elsemieke S. Levens, Amar D. Moes, Dirk-Jan A. R. Gevers, Tom J. G. van der Meer, Suzanne Brouwer, Hans T. de Jonge, Hendrik J. M. de Boer, Ynte S. Beuers, Ulrich H. W. van der Meer, Adriaan J. van den Berg, Aad P. Guichelaar, Maureen M. J. Drenth, Joost P. H. van Hoek, Bart

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Schlagwörter:	AIH Autoimmune hepatitis Autoimmune liver disease Tacrolimus Mycophenolate mofetil Randomised controlled trials Second-line treatment Complete biochemical response

Anmerkung:	© The Author(s) 2024

Übergeordnetes Werk:	Enthalten in: Trials - London : BioMed Central, 2000, 25(2024), 1 vom: 17. Jan.
Übergeordnetes Werk:	volume:25 ; year:2024 ; number:1 ; day:17 ; month:01

Links:	Volltext

DOI / URN:	10.1186/s13063-023-07832-w

Katalog-ID:	SPR054427037

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245	1	0	\|a 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
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520			\|a 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.
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allfields	10.1186/s13063-023-07832-w doi (DE-627)SPR054427037 (SPR)s13063-023-07832-w-e DE-627 ger DE-627 rakwb eng Stoelinga, Anna E. C. verfasserin (orcid)0000-0002-3110-924X aut 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 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 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. AIH (dpeaa)DE-He213 Autoimmune hepatitis (dpeaa)DE-He213 Autoimmune liver disease (dpeaa)DE-He213 Tacrolimus (dpeaa)DE-He213 Mycophenolate mofetil (dpeaa)DE-He213 Randomised controlled trials (dpeaa)DE-He213 Second-line treatment (dpeaa)DE-He213 Complete biochemical response (dpeaa)DE-He213 Tushuizen, Maarten E. aut van den Hout, Wilbert B. aut Girondo, Mar D. M. Rodriguez aut de Vries, Elsemieke S. aut Levens, Amar D. aut Moes, Dirk-Jan A. R. aut Gevers, Tom J. G. aut van der Meer, Suzanne aut Brouwer, Hans T. aut de Jonge, Hendrik J. M. aut de Boer, Ynte S. aut Beuers, Ulrich H. W. aut van der Meer, Adriaan J. aut van den Berg, Aad P. aut Guichelaar, Maureen M. J. aut Drenth, Joost P. H. aut van Hoek, Bart aut Enthalten in Trials London : BioMed Central, 2000 25(2024), 1 vom: 17. Jan. (DE-627)326173552 (DE-600)2040523-6 1745-6215 nnns volume:25 year:2024 number:1 day:17 month:01 https://dx.doi.org/10.1186/s13063-023-07832-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 25 2024 1 17 01
spelling	10.1186/s13063-023-07832-w doi (DE-627)SPR054427037 (SPR)s13063-023-07832-w-e DE-627 ger DE-627 rakwb eng Stoelinga, Anna E. C. verfasserin (orcid)0000-0002-3110-924X aut 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 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 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. AIH (dpeaa)DE-He213 Autoimmune hepatitis (dpeaa)DE-He213 Autoimmune liver disease (dpeaa)DE-He213 Tacrolimus (dpeaa)DE-He213 Mycophenolate mofetil (dpeaa)DE-He213 Randomised controlled trials (dpeaa)DE-He213 Second-line treatment (dpeaa)DE-He213 Complete biochemical response (dpeaa)DE-He213 Tushuizen, Maarten E. aut van den Hout, Wilbert B. aut Girondo, Mar D. M. Rodriguez aut de Vries, Elsemieke S. aut Levens, Amar D. aut Moes, Dirk-Jan A. R. aut Gevers, Tom J. G. aut van der Meer, Suzanne aut Brouwer, Hans T. aut de Jonge, Hendrik J. M. aut de Boer, Ynte S. aut Beuers, Ulrich H. W. aut van der Meer, Adriaan J. aut van den Berg, Aad P. aut Guichelaar, Maureen M. J. aut Drenth, Joost P. H. aut van Hoek, Bart aut Enthalten in Trials London : BioMed Central, 2000 25(2024), 1 vom: 17. Jan. (DE-627)326173552 (DE-600)2040523-6 1745-6215 nnns volume:25 year:2024 number:1 day:17 month:01 https://dx.doi.org/10.1186/s13063-023-07832-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 25 2024 1 17 01
allfields_unstemmed	10.1186/s13063-023-07832-w doi (DE-627)SPR054427037 (SPR)s13063-023-07832-w-e DE-627 ger DE-627 rakwb eng Stoelinga, Anna E. C. verfasserin (orcid)0000-0002-3110-924X aut 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 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 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. AIH (dpeaa)DE-He213 Autoimmune hepatitis (dpeaa)DE-He213 Autoimmune liver disease (dpeaa)DE-He213 Tacrolimus (dpeaa)DE-He213 Mycophenolate mofetil (dpeaa)DE-He213 Randomised controlled trials (dpeaa)DE-He213 Second-line treatment (dpeaa)DE-He213 Complete biochemical response (dpeaa)DE-He213 Tushuizen, Maarten E. aut van den Hout, Wilbert B. aut Girondo, Mar D. M. Rodriguez aut de Vries, Elsemieke S. aut Levens, Amar D. aut Moes, Dirk-Jan A. R. aut Gevers, Tom J. G. aut van der Meer, Suzanne aut Brouwer, Hans T. aut de Jonge, Hendrik J. M. aut de Boer, Ynte S. aut Beuers, Ulrich H. W. aut van der Meer, Adriaan J. aut van den Berg, Aad P. aut Guichelaar, Maureen M. J. aut Drenth, Joost P. H. aut van Hoek, Bart aut Enthalten in Trials London : BioMed Central, 2000 25(2024), 1 vom: 17. Jan. (DE-627)326173552 (DE-600)2040523-6 1745-6215 nnns volume:25 year:2024 number:1 day:17 month:01 https://dx.doi.org/10.1186/s13063-023-07832-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 25 2024 1 17 01
allfieldsGer	10.1186/s13063-023-07832-w doi (DE-627)SPR054427037 (SPR)s13063-023-07832-w-e DE-627 ger DE-627 rakwb eng Stoelinga, Anna E. C. verfasserin (orcid)0000-0002-3110-924X aut 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 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 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. AIH (dpeaa)DE-He213 Autoimmune hepatitis (dpeaa)DE-He213 Autoimmune liver disease (dpeaa)DE-He213 Tacrolimus (dpeaa)DE-He213 Mycophenolate mofetil (dpeaa)DE-He213 Randomised controlled trials (dpeaa)DE-He213 Second-line treatment (dpeaa)DE-He213 Complete biochemical response (dpeaa)DE-He213 Tushuizen, Maarten E. aut van den Hout, Wilbert B. aut Girondo, Mar D. M. Rodriguez aut de Vries, Elsemieke S. aut Levens, Amar D. aut Moes, Dirk-Jan A. R. aut Gevers, Tom J. G. aut van der Meer, Suzanne aut Brouwer, Hans T. aut de Jonge, Hendrik J. M. aut de Boer, Ynte S. aut Beuers, Ulrich H. W. aut van der Meer, Adriaan J. aut van den Berg, Aad P. aut Guichelaar, Maureen M. J. aut Drenth, Joost P. H. aut van Hoek, Bart aut Enthalten in Trials London : BioMed Central, 2000 25(2024), 1 vom: 17. Jan. (DE-627)326173552 (DE-600)2040523-6 1745-6215 nnns volume:25 year:2024 number:1 day:17 month:01 https://dx.doi.org/10.1186/s13063-023-07832-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 25 2024 1 17 01
allfieldsSound	10.1186/s13063-023-07832-w doi (DE-627)SPR054427037 (SPR)s13063-023-07832-w-e DE-627 ger DE-627 rakwb eng Stoelinga, Anna E. C. verfasserin (orcid)0000-0002-3110-924X aut 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 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 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. AIH (dpeaa)DE-He213 Autoimmune hepatitis (dpeaa)DE-He213 Autoimmune liver disease (dpeaa)DE-He213 Tacrolimus (dpeaa)DE-He213 Mycophenolate mofetil (dpeaa)DE-He213 Randomised controlled trials (dpeaa)DE-He213 Second-line treatment (dpeaa)DE-He213 Complete biochemical response (dpeaa)DE-He213 Tushuizen, Maarten E. aut van den Hout, Wilbert B. aut Girondo, Mar D. M. Rodriguez aut de Vries, Elsemieke S. aut Levens, Amar D. aut Moes, Dirk-Jan A. R. aut Gevers, Tom J. G. aut van der Meer, Suzanne aut Brouwer, Hans T. aut de Jonge, Hendrik J. M. aut de Boer, Ynte S. aut Beuers, Ulrich H. W. aut van der Meer, Adriaan J. aut van den Berg, Aad P. aut Guichelaar, Maureen M. J. aut Drenth, Joost P. H. aut van Hoek, Bart aut Enthalten in Trials London : BioMed Central, 2000 25(2024), 1 vom: 17. Jan. (DE-627)326173552 (DE-600)2040523-6 1745-6215 nnns volume:25 year:2024 number:1 day:17 month:01 https://dx.doi.org/10.1186/s13063-023-07832-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 25 2024 1 17 01
language	English
source	Enthalten in Trials 25(2024), 1 vom: 17. Jan. volume:25 year:2024 number:1 day:17 month:01
sourceStr	Enthalten in Trials 25(2024), 1 vom: 17. Jan. volume:25 year:2024 number:1 day:17 month:01
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	AIH Autoimmune hepatitis Autoimmune liver disease Tacrolimus Mycophenolate mofetil Randomised controlled trials Second-line treatment Complete biochemical response
isfreeaccess_bool	true
container_title	Trials
authorswithroles_txt_mv	Stoelinga, Anna E. C. @@aut@@ Tushuizen, Maarten E. @@aut@@ van den Hout, Wilbert B. @@aut@@ Girondo, Mar D. M. Rodriguez @@aut@@ de Vries, Elsemieke S. @@aut@@ Levens, Amar D. @@aut@@ Moes, Dirk-Jan A. R. @@aut@@ Gevers, Tom J. G. @@aut@@ van der Meer, Suzanne @@aut@@ Brouwer, Hans T. @@aut@@ de Jonge, Hendrik J. M. @@aut@@ de Boer, Ynte S. @@aut@@ Beuers, Ulrich H. W. @@aut@@ van der Meer, Adriaan J. @@aut@@ van den Berg, Aad P. @@aut@@ Guichelaar, Maureen M. J. @@aut@@ Drenth, Joost P. H. @@aut@@ van Hoek, Bart @@aut@@
publishDateDaySort_date	2024-01-17T00:00:00Z
hierarchy_top_id	326173552
id	SPR054427037
language_de	englisch
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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. 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author	Stoelinga, Anna E. C.
spellingShingle	Stoelinga, Anna E. C. misc AIH misc Autoimmune hepatitis misc Autoimmune liver disease misc Tacrolimus misc Mycophenolate mofetil misc Randomised controlled trials misc Second-line treatment misc Complete biochemical response 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
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topic_title	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 AIH (dpeaa)DE-He213 Autoimmune hepatitis (dpeaa)DE-He213 Autoimmune liver disease (dpeaa)DE-He213 Tacrolimus (dpeaa)DE-He213 Mycophenolate mofetil (dpeaa)DE-He213 Randomised controlled trials (dpeaa)DE-He213 Second-line treatment (dpeaa)DE-He213 Complete biochemical response (dpeaa)DE-He213
topic	misc AIH misc Autoimmune hepatitis misc Autoimmune liver disease misc Tacrolimus misc Mycophenolate mofetil misc Randomised controlled trials misc Second-line treatment misc Complete biochemical response
topic_unstemmed	misc AIH misc Autoimmune hepatitis misc Autoimmune liver disease misc Tacrolimus misc Mycophenolate mofetil misc Randomised controlled trials misc Second-line treatment misc Complete biochemical response
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title	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
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title_full	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
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author_browse	Stoelinga, Anna E. C. Tushuizen, Maarten E. van den Hout, Wilbert B. Girondo, Mar D. M. Rodriguez de Vries, Elsemieke S. Levens, Amar D. Moes, Dirk-Jan A. R. Gevers, Tom J. G. van der Meer, Suzanne Brouwer, Hans T. de Jonge, Hendrik J. M. de Boer, Ynte S. Beuers, Ulrich H. W. van der Meer, Adriaan J. van den Berg, Aad P. Guichelaar, Maureen M. J. Drenth, Joost P. H. van Hoek, Bart
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title_sort	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
title_auth	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
abstract	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. © The Author(s) 2024
abstractGer	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. © The Author(s) 2024
abstract_unstemmed	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. © The Author(s) 2024
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title_short	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
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C.</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-3110-924X</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">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</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2024</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s) 2024</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">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. 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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

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