E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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.
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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?
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E.2.2 | Secondary objectives of the trial |
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?
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 18 years or older - Mesalazine maintenance therapy >1 year - Quiescent disease (definition: CDAI <150) - Written informed consent |
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E.4 | Principal 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
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E.5 End points |
E.5.1 | 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.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial is the last visit of the last subject undergoing the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |