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Control Crohn Safe Trial (CoCroS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03917303
Recruitment Status : Recruiting
First Posted : April 17, 2019
Last Update Posted : July 23, 2020
Sponsor:
Collaborators:
Maastricht University
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
Maastricht University Medical Center

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


Condition or disease Intervention/treatment Phase
Crohn Disease Inflammatory Bowel Diseases Drug: Adalimumab Drug: standard step-up care Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 158 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multicenter randomised controlled trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Control Crohn Safe With Episodic Adalimumab Monotherapy as First Line Treatment Study.
Actual Study Start Date : December 23, 2019
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : September 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease
Drug Information available for: Adalimumab

Arm Intervention/treatment
Active Comparator: Adalimumab
Episodic adalimumab monotherapy as first line treatment for 6 months
Drug: Adalimumab
episodic treatment with subcutaneous adalimumab for 6 months
Other Name: Humira

Active Comparator: Standard step-up care
Step-up care as first line treatment, starting with corticosteroids.
Drug: standard step-up care
conventional step-up care starting with corticosteroids




Primary Outcome Measures :
  1. Number of yearly-quarters of corticosteroid free remission as a measure of treatment efficacy [ Time Frame: at week 96 ]
    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.


Secondary Outcome Measures :
  1. Cumulative structural bowel damage as a measure of disease progression [ Time Frame: at week 96 ]

    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.


  2. Incidence of drug related serious adverse events [ Time Frame: at week 24, 48 and 96 ]
    Drug related serious adverse events

  3. Incidence of serious disease related adverse events [ Time Frame: at week 24, 48 and 96 ]
    Crohn disease related hospitalisation and surgery

  4. Integer amount of direct health care costs (in €) [ Time Frame: at week 96 ]

    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.


  5. Integer amount of indirect health care costs (in €) [ Time Frame: at week 96 ]

    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.


  6. Corticosteroid use [ Time Frame: at week 24, 48 and 96 ]
    Cumulative corticosteroid dose

  7. Endoscopic remission as assessed by SES-CD [ Time Frame: at week 24 ]
    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.

  8. Time to remission [ Time Frame: at week 96 ]
    Time to remission

  9. Quality of life as assessed by QoL EQ-5D-5L questionnaire [ Time Frame: at week 24, 48 and 96 ]

    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.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 thiopurines and biologicals
  • Sufficient knowledge of Dutch language
  • 18 years old ≤ 70 years old
  • Smartphone with internet access

Exclusion Criteria:

  • Use of corticosteroids for a duration longer than 4 months in the year before screening
  • Malignancy in 5 years before treatment. Exception is adequately treated non-melanoma skin cancer
  • Perianal fistula at screening
  • Severe disease requiring hospitalisation at screening
  • Contra-indication for TNF-blockers or immunosuppressive agents
  • Contra-indication for MRI-enterography
  • Patients with short bowel syndrome or an ostomy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03917303


Contacts
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Contact: M J Pierik, MD, PhD +31 43 387 4362 m.pierik@mumc.nl
Contact: L M Janssen, MD laura.janssen@maastrichtuniversity.nl

Locations
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Netherlands
Maastricht University Medical Centre+ Recruiting
Maastricht, Netherlands
Contact: L Janssen    +31433884190    laura.janssen@maastrichtuniversity.nl   
Contact: M Pierik    +31433875021    m.pierik@mumc.nl   
Principal Investigator: M. Pierik         
Sub-Investigator: L. Janssen         
Sub-Investigator: J. Haans         
Zuyderland Medical Center Recruiting
Sittard, Netherlands
Contact: AA van Bodegraven         
Principal Investigator: AA van Bodegraven         
Sub-Investigator: M Romberg-Camps         
Sponsors and Collaborators
Maastricht University Medical Center
Maastricht University
ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
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Principal Investigator: M J Pierik, MD, PhD Maastricht University Medical Centre
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Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT03917303    
Other Study ID Numbers: NL64005.068.18
First Posted: April 17, 2019    Key Record Dates
Last Update Posted: July 23, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data will be made available to other researchers on demand. Patients will be asked to give informed consent to share the collected data with third parties for future research.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Adalimumab
Anti-Inflammatory Agents
Antirheumatic Agents