Clinical trial NCT03917303: Control Crohn Safe Trial
Official title: Control Crohn Safe With Episodic Adalimumab Monotherapy as First Line Treatment Study.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Crohn Disease
Inflammatory Bowel Diseases
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Maastricht University
name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2019-04-17
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter randomised controlled trial
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of yearly-quarters of corticosteroid free remission as a measure of treatment efficacy
timeFrame: at week 96
Secondary outcomes:
measure: Cumulative structural bowel damage as a measure of disease progression
timeFrame: at week 96
measure: Incidence of drug related serious adverse events
timeFrame: at week 24, 48 and 96
measure: Incidence of serious disease related adverse events
timeFrame: at week 24, 48 and 96
measure: Integer amount of direct health care costs (in €)
timeFrame: at week 96
measure: Integer amount of indirect health care costs (in €)
timeFrame: at week 96
measure: Corticosteroid use
timeFrame: at week 24, 48 and 96
measure: Endoscopic remission as assessed by SES-CD
timeFrame: at week 24
measure: Time to remission
timeFrame: at week 96
measure: Quality of life as assessed by QoL EQ-5D-5L questionnaire
timeFrame: at week 24, 48 and 96
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre+
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis
city: Roermond
country: Netherlands
facility: Laurentius Ziekenhuis
city: Sittard
country: Netherlands
facility: Zuyderland Medical Center
city: Veldhoven
country: Netherlands
facility: Máxima Medisch Centrum
city: Venlo
country: Netherlands
facility: VieCuri
Study officials:
affiliation: Maastricht University Medical Centre
name: M J Pierik, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.