A randomized controlled withdrawal trial in Crohn's disease patients in long-term remission on mesalazine: the CROWN study

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-011220-62-NL
• Date of registration: 13/07/2009
• Prospective Registration: Yes
• Primary sponsor: University Medical Center Utrecht
• Public title: A randomized controlled withdrawal trial in Crohn's disease patients in long-term remission on mesalazine: the CROWN study
• Scientific title: A randomized controlled withdrawal trial in Crohn's disease patients in long-term remission on mesalazine: the CROWN study
• Date of first enrolment: 26/10/2009
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-011220-62
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: no treatment

Countries of recruitment

Netherlands

Key inclusion & exclusion criteria

Inclusion criteria:
- 18 years or older
- Mesalazine maintenance therapy >1 year
- Quiescent disease (definition: CDAI <150)
- Written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Flare-up(s) of CD within 12 months preceding inclusion
- Treatment with prednisone, budesonide, infliximab, adalumimab of ceroluzimab within 12 months of inclusion
- Treatment with methotrexate, mercaptopurine or azathioprine, when initiated within 6 months prior to inclusion
- Extra-intestinal CD manifestations such as fistulas or pyoderma gangrenosum demanding induction therapy
- Treatment with enteral or parenteral feeding within 6 months prior to inclusion
- Treatment with metronidazole, ciprofloxacin, rectal steroids or rectal aminosalicylates within 12 months prior to inclusion
- Previous ileo-colorectal resection, such as small bowel resections >100 cm, total proctocolectomy, subtotal colectomy, colostomy or ileostomy
- Primary sclerosing cholangitis (PSC)
- Hypersensitivity to mesalazine
- Disorders, which are likely to require systemic steroids (e.g. asthma)
- Abnormalities in liver function tests (definition: 2x upper limit of normal value of ALAT. Normal values ALAT: > 45 U/L (men) of >35 U/L (women)
- Abnormalities in kidney function tests (definition: creatinin > 120 µmol/L (men) or
>103 µmol/L (women)
- Dysplasia or neoplasia of the colon
- Pregnant or lactating women



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

1. Patients with a diagnosis of quiscent (CDAI < 150) Crohn's Disease (CD) according to established clinical, endoscopic, radiological and histological criteria. 2. Patients will be aged 18 years or older. 3. Patients with mesalazine maintenance therapy > 1 year.
MedDRA version: 9.1 Level: LLT Classification code 10011401 Term: Crohn's disease

Intervention(s)

Product Name: mesalazine
Pharmaceutical Form: Tablet
INN or Proposed INN: mesalazine
CAS Number: 65-49-6
Other descriptive name: AMINOSALICYLIC ACID
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 3000-3200

Primary Outcome(s)

Main Objective: 1. What is the effect of stopping mesalazine in the maintenance setting of patients with quiescent CD?

2. Can subgroups of CD patients, for example based on prior treatment (medical vs. surgical), localization of disease, disease behavior (number of prior relapses and/or development of complications, such as fistulas or strictures) or co-medication be identified, which benefit most from mesalazine maintenance therapy?

3. Is mesalazine cost-effective in a subgroup of CD patients?

Secondary Objective: 1. How does stopping of mesalazine affect quality of life of CD patients?

2. Does compliance to mesalazine affect outcome with regard to disease activity and quality of life?

Primary end point(s): The primary endpoints are:

1. The proportion of patients who experience a clinical relapse during the 18 months follow-up period, defined as:
- CDAI score above 250 or a score between 150-250 in 3 consecutive weeks with an increase of at least 75 points above the baseline value, and/or;
- Need to perform surgery, and/or;
- Adjustment of CD-related therapy during follow-up, for example by the addition of steroids, infliximab, methotrexate, 6-mercaptopurine or azathioprine.

2. Cost-effectiveness
- To assess cost-effectiveness we will investigate total costs of mesalazine
versus no mesalazine maintenance in CD patients. The economic evaluation will be performed in accordance with the Dutch guidelines20. We will take a societal perspective, and include health care costs and patient costs (e.g. work absence and travel costs). For the calculation of the health care costs of the two different treatment strategies (i.e. mesalazine or no mesalazine maintenance), we will distinguish medication costs, intramural costs (inpatients days, general practitioner activities, medical treatment) and extramural costs (home care, general practioner). Patient costs will include costs of absence from work or school (sick leave), travel costs, and time costs. Real medical costs will be calculated by multiplying the volumes of health care use with the corresponding cost prices. Unit costs of health care consumption and patient costs will be estimated according to Dutch guidelines20. Data on the volume of care will be available from hospital information systems in the participating hospitals. Data on volume of outpatient care as well as all data needed for the estimation of non-medical and indirect costs will be collected from the questionnaires filled out by all patients.

Secondary ID(s)

80-82310-98-09098