Adalimumab on Preventing Post-chirurgic Recurrence on Crohn´s Disease

Study Overview
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Brief Summary
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The present study objective is evaluate Adalimumab efficacy versus Azathioprine efficacy on prevention of endoscopic recurrence (Rutgeerts Index= 2b, 3 or 4) in Crohn´s Disease patients after 52 weeks of treatment.

Official Title
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Adalimumab on Preventing Postoperative Recurrence of Crohn's Disease

Conditions
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Crohn´s Disease

Intervention / Treatment
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* Drug: Metronidazole
* Drug: Metronidazole
* Drug: Azathioprine
* Drug: Adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years of age at the time of signing informed consent. Patients with Crohn's disease who have undergone an ileocecal/ileocolic resection (L1 or L3). The study and the treatment must be initiated within the two first weeks after the resection (+/- 5 days). Patients with surgical reconstruction by ileocolic anastomosis. Women of childbearing age must not be breastfeeding and must have a negative urine pregnancy test and must agree to use contraceptive methods with a <1% failure rate (e.g., sexual abstinence, oral contraceptives, double barrier methods, intrauterine devices), unless they only have one partner who is sterile. Patients who have signed and dated the informed consent form before performing any specific screening study procedure. Exclusion Criteria: Resection that requieres Temporal ileostomy. Urgency resection which doesn´t permit the initial assessment protocol completion. Resection due to inactive short indolent stenosis (<10 cm). Resection with mucosal macroscopic residual disease in anastomosis. Previous intolerance or adverse reaction (moderate or severe) to adalimumab or azathioprine. Any contraindications or unwillingness to perform the scheduled colonoscopies or resonances. Contraindications to Adalimumab treatment, among which the following are included: active tuberculosis, severe infections such as sepsis or opportunistic infections, moderate or severe heart failure (NYHA class III or IV), central nervous system demyelinating diseases, history of malignant neoplasm or autoimmune diseases. Severe associated Extraintestinal manifestations. Previous postoperative recurrence prevention treatments with adalimumab, asathiprine o mercaptopurine which resulted in failure. Any other disease or patient condition that according to investigator criteria, inadequates patient´s participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metronidazole + Azathioprine.<br>Metronidazole, oral intake. 250 mg/8h. 3 months. Azathioprine, 2.5 mg/weight kg/day, oral intake. All study. | Drug: Metronidazole<br>* Metronidazole: 250 mg/8h. 3 months.<br>* Other names: Flagyl (Metronidazole);Drug: Azathioprine<br>* Azathioprine: 2.5 mg/kg of weight/day. 3 months.<br>* Other names: Imurel (Azathioprine);|
| Active Comparator: Metronidazole + Adalimumab<br>Metronidazole Oral Intake. 250 mg/8h. During 3 months. Adalimumab Subcutaneous 160 mg and 80 mg 2wk. Then 40 mg during 2wk as maintenance. | Drug: Metronidazole<br>* Metronidazole 250 mg/8h 3 months<br>* Other names: Flagyl (Metronidazole);Drug: Adalimumab<br>* Adalimumab 160 mg then 80 mg. After 2 wk: 40 mg as maintenance.<br>* Other names: Humira (Adalimumab);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of endoscopic recurrences | Evaluation of the effectiveness on prevention of endoscopic recurrence evaluated as changes in the Rutgeerts Index. | 52 weeks after the begin of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Crohns´disease remission | % of patients showing clinical remission after 24 and 52 weeks of adalimumab vs azathioprin treatment | 24 weeks | 
| Number of postsurgical recurrences | Evaluation of the Adalimumab efficiency on preventing postsurgical recurrence with Magnetic Resonance Enterography | 52 week | 
| number of hospitalized patients | Comparing hospitalization percentage in patients using adalimumab or azathioprin after 52 weeks of treatment | 52 weeks | 
| Concentration of activity markers | Evaluating changes in markers such as reactive c-protein, variable surface glycoprotein , faecal calprotectin, etc. | 24 weeks | 
| Number of surgeries | Comparing % of patients who needs surgery on Adalimumab vs Azatioprine | Until 52 week | 
| SIBDQ and EuroQOL indexes | Quality of life | 24 Weeks | 
| Number of Adverse event reports | Comparison of safety of Adalimumab versus Azatioprine. | 52 weeks | 
| Number of Crohns´disease remission | % of patients showing clinical remission after 24 and 52 weeks of adalimumab vs azatioprine treatment | 52 weeks | 
| Concentration of activity markers | Evaluating changes in markers such as reactive c-protein, VSG, faecal calprotectine, etc | 52 weeks | 
| SIBDQ and EuroQOL indexes | Quality of life | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn´s disease, Metronidazole, Azathioprine, Adalimumab, post-chirurgic recurrence