Control Crohn Safe Trial

Crohn Disease Clinical Trial

— CoCroS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03917303
• Other study ID #: NL64005.068.18
• Status: Recruiting
• Phase: Phase 4
• Start date: December 23, 2019
• Est. completion date: September 2026

Study information

• Verified date: September 2022
• Source: Maastricht University Medical Center
• Contact: M J Pierik, MD, PhD
• Phone: +31 43 387 4362
• Email: m.pierik[@]mumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 158
• Est. completion date: September 2026
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease
• Inflammatory Bowel Diseases

Intervention

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

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Centre+	Maastricht
Netherlands	St. Antonius Ziekenhuis	Nieuwegein
Netherlands	Laurentius Ziekenhuis	Roermond
Netherlands	Zuyderland Medical Center	Sittard
Netherlands	Máxima Medisch Centrum	Veldhoven
Netherlands	VieCuri	Venlo

Sponsors (3)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Maastricht University, ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of yearly-quarters of corticosteroid free remission as a measure of treatment efficacy	Remission is defined as combined clinical (MIAH scores (=3)) and biochemical (C-reactive protein =5 mg/L (i.e. within normal range) and fecal calprotectin = 200 µg/g) remission.	at week 96
Secondary	Cumulative structural bowel damage as a measure of disease progression	Disease progression on MRI-enterography based on the Lémann score (Crohn's Disease Digestive Damage Score); the Lémann score is an instrument to measure cumulative structural bowel damage in Crohn's disease. The score takes into account the damage location (upper digestive tract, small bowel, colon/rectum and anal/perianal), extent and severity.; Grades 0 (normal) to 3 (maximal) are given to each segment of the digestive tract, with grade 3 representing the most damage, or resection/bypass.	at week 96
Secondary	Incidence of drug related serious adverse events	Drug related serious adverse events	at week 24, 48 and 96
Secondary	Incidence of serious disease related adverse events	Crohn disease related hospitalisation and surgery	at week 24, 48 and 96
Secondary	Integer amount of direct health care costs (in €)	Direct costs include expenses for medication, diagnostic procedures, number of outpatient clinic visits, hospitalisations and surgeries.; Direct costs will be combined with indirect costs to report total health care costs.	at week 96
Secondary	Integer amount of indirect health care costs (in €)	Indirect costs consist of costs due to presenteeism and absenteeism and are assessed by questionnaires in the telemedicine tool myIBDcoach used for monitoring of IBD patients.; Indirect costs will be combined with direct costs to report total health care costs.	at week 96
Secondary	Corticosteroid use	Cumulative corticosteroid dose	at week 24, 48 and 96
Secondary	Endoscopic remission as assessed by SES-CD	Proportion of endoscopic remission based on SES-CD (simple endoscopic score for CD). Endoscopic remission is defined as a score below 3 and the absence of ulcers.	at week 24
Secondary	Time to remission	Time to remission	at week 96
Secondary	Quality of life as assessed by QoL EQ-5D-5L questionnaire	Quality of life as assessed by the QoL EQ-5D-5L questionnaire in which the level of severity is chosen for five domains (mobility, self-care, usual activities, pain, anxiety/depression).; A higher level (maximal 5) indicates more severe problems in that particular domain.	at week 24, 48 and 96