Control Crohn Safe Trial

Phase 4RecruitingNCT03917303

Maastricht University Medical Center158 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (6)

Maastricht University Medical Centre+

Maastricht, Netherlands

RECRUITING

St. Antonius Ziekenhuis

Nieuwegein, Netherlands

RECRUITING

Laurentius Ziekenhuis

Roermond, Netherlands

RECRUITING

Zuyderland Medical Center

Sittard, Netherlands

RECRUITING

Máxima Medisch Centrum

Veldhoven, Netherlands

RECRUITING

VieCuri

Venlo, Netherlands

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: at week 96

Secondary Outcomes

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.

Time frame: at week 96

Incidence of drug related serious adverse events

Drug related serious adverse events

Time frame: at week 24, 48 and 96

Incidence of serious disease related adverse events

Crohn disease related hospitalisation and surgery

Time frame: at week 24, 48 and 96

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.

Time frame: at week 96

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.

Time frame: at week 96

Corticosteroid use

Cumulative corticosteroid dose

Time frame: at week 24, 48 and 96

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.

Time frame: at week 24

Time to remission

Time frame: at week 96

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.

Time frame: at week 24, 48 and 96

Control Crohn Safe Trial

Overview

Conditions

Interventions

Eligibility

Locations (6)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts