Control Crohn Safe Trial

Официальное название

Control Crohn Safe With Episodic Adalimumab Monotherapy as First Line Treatment Study.

Обзор

Crohn's disease (CD) is a chronic disease with a heterogeneous clinical presentation, relapse rate and treatment response. Insufficient control of mucosal inflammation results in irreversible bowel damage and complications and at present no markers are available to predict such a complicated disease course at diagnosis. Therefore, to prevent overtreatment of low risk patients, step-up treatment with subsequent introduction of corticosteroids, thiopurines maintenance and TNF-blockers if a previous category fails is standard care. Combination treatment with thiopurines and a TNF-blocker is more effective than monotherapy but associated with a higher risk for infectious complications. Landmark studies convincingly showed an improved long-term outcome if the TNF-blocker infliximab is introduced early after diagnosis. The standard step-care approach thus prolongs steroid exposure and delays start of disease modifying biologicals in high risks patients. Given the higher efficacy of combination therapy with a thiopurine of infliximab and potential allergic reactions and lower response rates after re-initiation of this chimeric biological, temporary monotherapy with this TNF-blocker has not been studied as first line treatment before. Adalimumab is a humanised monoclonal antibody and subsequently, combination therapy of adalimumab + thiopurines has only a marginal effect on anti-drug anti-body formation. Furthermore, combination therapy with adalimumab does not enhance the clinical response. Therefore, periodic treatment with adalimumab in combination with close monitoring after drug-discontinuation, in newly diagnosed CD might improve outcome, reduce drug-related side effects while still preventing overtreatment. The aim of this study is to compare the long-term efficacy and safety of periodic adalimumab as initial treatment in newly diagnosed CD patients compared to standard step-care with corticosteroid/budesonide as the initial treatment

Вмешательства

• Препарат Adalimumab
  episodic treatment with subcutaneous adalimumab for 6 months
• Препарат standard step-up care
  conventional step-up care starting with corticosteroids

Первичные конечные точки

• Number of yearly-quarters of corticosteroid free remission as a measure of treatment efficacy [Срок оценки: at week 96]

Вторичные конечные точки (9)

• Cumulative structural bowel damage as a measure of disease progression [Срок оценки: at week 96]
• Incidence of drug related serious adverse events [Срок оценки: at week 24, 48 and 96]
• Incidence of serious disease related adverse events [Срок оценки: at week 24, 48 and 96]
• Integer amount of direct health care costs (in €) [Срок оценки: at week 96]
• Integer amount of indirect health care costs (in €) [Срок оценки: at week 96]
• Corticosteroid use [Срок оценки: at week 24, 48 and 96]
• Endoscopic remission as assessed by SES-CD [Срок оценки: at week 24]
• Time to remission [Срок оценки: at week 96]
• Quality of life as assessed by QoL EQ-5D-5L questionnaire [Срок оценки: at week 24, 48 and 96]

Критерии участия

Критерии включения

• Newly diagnosed CD patients or CD patients with a flare, visiting the outpatient clinic or endoscopy ward of the participating centres
• CD diagnosis according to ECCO-guidelines + complete ileo-colonoscopy + complete small bowel imaging at diagnosis (MRI or CT-enterography )
• Naïve to biologicals
• Sufficient knowledge of Dutch language
• 18 years old ≤ 70 years old
• Smartphone with internet access
• Use of myIBDcoach or willingness to start using myIBDcoach

Критерии исключения

• Use of prednisone for longer than 4 weeks in the year before screening
• Use of budesonide (≥6 mg daily) for a duration longer than 3 months in the year before screening
• Use of thiopurines in the 3 years before screening
• Indication for primary treatment with biologicals or surgery
• Malignancy in 5 years before treatment. Exception is adequately treated non-melanoma skin cancer
• Contra-indication for TNF-blockers or immunosuppressive agents
• Contra-indication for MRI- and CT-enterography
• Patients with short bowel syndrome or an ostomy

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Нидерланды · 6 центров

• Maastricht University Medical Centre+ — Maastricht
• St. Antonius Ziekenhuis — Nieuwegein
• Laurentius Ziekenhuis — Roermond
• Zuyderland Medical Center — Sittard
• Máxima Medisch Centrum — Veldhoven
• VieCuri — Venlo

Публикации

• Janssen L, Romberg-Camps M, van Bodegraven A, Haans J, Aquarius M, Boekema P, Munnecom T, Brandts L, Joore M, Masclee A, Jonkers D, Pierik M. Control Crohn Safe with episodic adalimumab monotherapy as first-line treatment study (CoCroS): study protocol for a randomised controlled trial. BMJ Open. 2021 May 4;11(5):e042885. doi: 10.1136/bmjopen-2020-042885. PMID 33947729

Идентификаторы

NCT: NCT03917303 · NL64005.068.18

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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