Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial
Introduction Symptoms, endoscopy and histology have been proposed as therapeutic targets in ulcerative colitis (UC). Observational studies suggest that the achievement of histologic remission may be associated with a lower risk of complications, compared with the achievement of endoscopic remission...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2024-07-01
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| Series: | BMJ Open Gastroenterology |
| Online Access: | https://bmjopengastro.bmj.com/content/11/1/e001218.full |
| _version_ | 1826806706786533376 |
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| author | Shaji Sebastian Silvio Danese Séverine Vermeire Simon Travis Jean-Frederic Colombel Brian G Feagan Vipul Jairath Guangyong Zou Geert R D’Haens William J Sandborn Gordon W Moran Christopher Ma Peter Bossuyt Daniel Green Mark S Silverberg Maria Kłopocka Marek Horynski Stefanie C McFarlane Zhongya Wang Shashi Adsul Marcelo Freire Gabriela Radulescu Julie Sigler Jurij Hanžel Rocio Sedano Naveen Arya Melanie Beaton William Harlan Rima Petroniene Lukasz Wolanski |
| author_facet | Shaji Sebastian Silvio Danese Séverine Vermeire Simon Travis Jean-Frederic Colombel Brian G Feagan Vipul Jairath Guangyong Zou Geert R D’Haens William J Sandborn Gordon W Moran Christopher Ma Peter Bossuyt Daniel Green Mark S Silverberg Maria Kłopocka Marek Horynski Stefanie C McFarlane Zhongya Wang Shashi Adsul Marcelo Freire Gabriela Radulescu Julie Sigler Jurij Hanžel Rocio Sedano Naveen Arya Melanie Beaton William Harlan Rima Petroniene Lukasz Wolanski |
| author_sort | Shaji Sebastian |
| collection | DOAJ |
| description | Introduction Symptoms, endoscopy and histology have been proposed as therapeutic targets in ulcerative colitis (UC). Observational studies suggest that the achievement of histologic remission may be associated with a lower risk of complications, compared with the achievement of endoscopic remission alone. The actiVE ulcerative colitis, a RanDomIsed Controlled Trial (VERDICT) aims to determine the optimal treatment target in patients with UC.Methods and analysis In this multicentre, prospective randomised study, 660 patients with moderate to severe UC (Mayo rectal bleeding subscore [RBS] ≥1; Mayo endoscopic score [MES] ≥2) are randomly assigned to three treatment targets: corticosteroid-free symptomatic remission (Mayo RBS=0) (group 1); corticosteroid-free endoscopic remission (MES ≤1) and symptomatic remission (group 2); or corticosteroid-free histologic remission (Geboes score <2B.0), endoscopic remission and symptomatic remission (group 3). Treatment is escalated using vedolizumab according to a treatment algorithm that is dependent on the patient’s baseline UC therapy until the target is achieved at weeks 16, 32 or 48. The primary outcome, the time from target achievement to a UC-related complication, will be compared between groups 1 and 3 using a Cox proportional hazards model.Ethics and dissemination The study was approved by ethics committees at the country level or at individual sites as per individual country requirements. A full list of ethics committees is available on request. Study results will be disseminated in peer-reviewed journals and at scientific meetings.Trial registration number EudraCT: 2019-002485-12; NCT04259138. |
| first_indexed | 2024-03-08T04:08:45Z |
| format | Article |
| id | doaj.art-90b48a3e247b434da3279f2d6dcef059 |
| institution | Directory Open Access Journal |
| issn | 2054-4774 |
| language | English |
| last_indexed | 2025-02-16T00:16:13Z |
| publishDate | 2024-07-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open Gastroenterology |
| spelling | doaj.art-90b48a3e247b434da3279f2d6dcef0592025-02-12T10:05:10ZengBMJ Publishing GroupBMJ Open Gastroenterology2054-47742024-07-0111110.1136/bmjgast-2023-001218Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trialShaji Sebastian0Silvio Danese1Séverine Vermeire2Simon Travis3Jean-Frederic Colombel4Brian G Feagan5Vipul Jairath6Guangyong Zou7Geert R D’Haens8William J Sandborn9Gordon W Moran10Christopher Ma11Peter Bossuyt12Daniel Green13Mark S Silverberg14Maria Kłopocka15Marek Horynski16Stefanie C McFarlane17Zhongya Wang18Shashi Adsul19Marcelo Freire20Gabriela Radulescu21Julie Sigler22Jurij Hanžel23Rocio Sedano24Naveen Arya25Melanie Beaton26William Harlan27Rima Petroniene28Lukasz Wolanski29Department of Gastroenterology, Hull University Teaching Hospitals NHS Trust, Hull, East Riding of Yorkshire, UK41 Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milano, Italy14 Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium8 Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Biomedical Research Centre, University of Oxford, Oxford, UK4 The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA1 Department of Medicine, Division of Gastroenterology; Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada1 Department of Medicine, Division of Gastroenterology; Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada2 Alimentiv Inc, London, Ontario, Canada6 Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam, The Netherlands11 Division of Gastroenterology, University of California San Diego, La Jolla, California, USA17 Gastroenterology, NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals, Nottingham, UK16 Division of Gastroenterology & Hepatology, Cumming School of Medicine; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, CanadaImelda GI Clinical Research Center, Imelda Hospital, Bonheiden, BelgiumYaqrit Discovery Limited. The Elms Courtyard, Bromesberrow, Ledbury, UK16 Division of Gastroenterology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada24 Department of Gastroenterology and Nutritional Disorders, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland23 Endoskopia Sp. z.o.o, Sopot, Poland2 Alimentiv Inc, London, Ontario, Canada2 Alimentiv Inc, London, Ontario, Canada4 Takeda Pharmaceuticals, Cambridge, Massachusetts, USA4 Takeda Pharmaceuticals, Cambridge, Massachusetts, USA2 Alimentiv Inc, London, Ontario, Canada2 Alimentiv Inc, London, Ontario, Canada2 Alimentiv Inc, London, Ontario, Canada2 Alimentiv Inc, London, Ontario, Canada18 ABP Research Services Corp, Oakville, Ontario, Canada17 Department of Medicine, Division of Gastroenterology, University of Western Ontario, London, Ontario, Canada22 Asheville Gastroenterology Associates, Asheville, North Carolina, USA26 Barrie GI Associates Inc, Barrie, Ontario, Canada28 Gastroenterological Department, Samodzielny Publiczny Zakład Opieki Zdrowotnej w Łęcznej, Łęcznej, PolandIntroduction Symptoms, endoscopy and histology have been proposed as therapeutic targets in ulcerative colitis (UC). Observational studies suggest that the achievement of histologic remission may be associated with a lower risk of complications, compared with the achievement of endoscopic remission alone. The actiVE ulcerative colitis, a RanDomIsed Controlled Trial (VERDICT) aims to determine the optimal treatment target in patients with UC.Methods and analysis In this multicentre, prospective randomised study, 660 patients with moderate to severe UC (Mayo rectal bleeding subscore [RBS] ≥1; Mayo endoscopic score [MES] ≥2) are randomly assigned to three treatment targets: corticosteroid-free symptomatic remission (Mayo RBS=0) (group 1); corticosteroid-free endoscopic remission (MES ≤1) and symptomatic remission (group 2); or corticosteroid-free histologic remission (Geboes score <2B.0), endoscopic remission and symptomatic remission (group 3). Treatment is escalated using vedolizumab according to a treatment algorithm that is dependent on the patient’s baseline UC therapy until the target is achieved at weeks 16, 32 or 48. The primary outcome, the time from target achievement to a UC-related complication, will be compared between groups 1 and 3 using a Cox proportional hazards model.Ethics and dissemination The study was approved by ethics committees at the country level or at individual sites as per individual country requirements. A full list of ethics committees is available on request. Study results will be disseminated in peer-reviewed journals and at scientific meetings.Trial registration number EudraCT: 2019-002485-12; NCT04259138.https://bmjopengastro.bmj.com/content/11/1/e001218.full |
| spellingShingle | Shaji Sebastian Silvio Danese Séverine Vermeire Simon Travis Jean-Frederic Colombel Brian G Feagan Vipul Jairath Guangyong Zou Geert R D’Haens William J Sandborn Gordon W Moran Christopher Ma Peter Bossuyt Daniel Green Mark S Silverberg Maria Kłopocka Marek Horynski Stefanie C McFarlane Zhongya Wang Shashi Adsul Marcelo Freire Gabriela Radulescu Julie Sigler Jurij Hanžel Rocio Sedano Naveen Arya Melanie Beaton William Harlan Rima Petroniene Lukasz Wolanski Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial BMJ Open Gastroenterology |
| title | Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial |
| title_full | Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial |
| title_fullStr | Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial |
| title_full_unstemmed | Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial |
| title_short | Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial |
| title_sort | determining the optimal treatment target in patients with ulcerative colitis rationale design protocol and interim analysis for the randomised controlled verdict trial |
| url | https://bmjopengastro.bmj.com/content/11/1/e001218.full |
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