Evaluation of Adherent Invasive E. Coli Eradication in Adult Crohn Disease

Study Overview
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Brief Summary
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The primary objective of this trial is to assess whether a 12-week treatment with Ciprofloxacin and Rifaximin is superior to placebo to obtain endoscopic remission in adherent-invasive E. coli (AIEC)-colonized patients with ileal Crohn disease (CD), with or without involvement of the caecum or the right colon.

Official Title
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Multicenter Double Blind Randomized Clinical Trial Assessing the Benefit of Adherent Invasive E. Coli Eradication in Adult Ileal and Ileo-colonic Crohn Disease

Conditions
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Crohn Disease, Adherent-invasive E. Coli

Intervention / Treatment
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* Drug: Ciprofloxacin
* Drug: Rifaximin
* Drug: Ciprofloxacin Placebo
* Drug: Rifaximin Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CD of the ileum, with or without involvement of the caecum or the right colon Colonoscopy showing active lesions defined by a CDEISm score >6 Informed consent to participate in this study Prescription of steroid treatments : Budesonide, Prednisone (or Prednisolone) independently from entry in study Patients who respond to budesonide (initial dose 9 mg/d) or prednisone or prednisolone (initial dose 40 mg/d), defined as a 70 points decrease in CDAI between the pre-inclusion and the inclusion visit, Patients colonized with AIEC on initial ileal biopsies. Exclusion Criteria: Ileal stenosis that cannot be crossed by the endoscope, Infliximab treatment received less than 8 weeks before inclusion in this study, Adalimumab treatment received less than 4 weeks before inclusion in this study, Vedolizumab treatment received less than 8 weeks before inclusion in the study, Hypersensitivity to Ciprofloxacin, to other quinolones, or to any of the excipients (cellulose microcrystalline, crospovidone, maize starch, magnesium stearate, silica colloidal anhydrous,, hypromellose titanium dioxide E171, macrogol 4000,), Tizanidine, Probenecid, Theophylline, Xanthine derivatives, Phenytoin, oral anticoagulants, and Ropinirole treatment, Hypersensitivity to Rifaximin, or to any excipients (sodium starch glycolate type A, glycerol distearate, colloidal anhydrous silica, talc, microcrystalline cellulose, hypromellose, titanium dioxide, disodium edentate, propylene glycol, red iron oxide E172), Previous extensive ileal surgery (≥ 1 meter as measured on the pathology and/or surgical report), Short bowel syndrome, Need for an intestinal resection for fistula, abscess or intestinal obstruction, Renal failure (creatinine clearance<30 mL/min/1.73m2), Liver failure (V factor<50%), Past history of epilepsy, No health insurance, Pregnant or lactating women, Refusal to have a double effective contraception, Patients already included in a biomedical research other than an observational study (e.g: registry, cohort).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental arm<br>oral Ciprofloxacin 500 mg bid and oral Rifaximin 800 mg bid for 12 weeks | Drug: Ciprofloxacin<br>* oral Ciprofloxacin 500 mg bis in die (bid) for 12 weeks<br>Drug: Rifaximin<br>* oral Rifaximin 800 mg bid for 12 weeks<br>|
| Placebo Comparator: Control arm<br>a placebo of Ciprofloxacin bid and a placebo of Rifaximin bid for 12 weeks | Drug: Ciprofloxacin Placebo<br>* a placebo of Ciprofloxacin bid for 12 weeks<br>Drug: Rifaximin Placebo<br>* a placebo of Rifaximin bid for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with Endoscopic Endoscopic Index of Severity (CDEISm)< 6 and a decrease in CDEISm ≥ 3 | (assessed within each site quotation), defined by the modified Crohn's Disease Endoscopic Index of Severity (CDEISm)< 6 and a decrease in CDEISm ≥ 3, as compared to baseline values. | week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean variation of CDEISm | assessed by centralized, anonymous and blinded reading of ileocolonoscopies | week 12 | 
| Complete endoscopic remission | assessed by centralized, anonymous and blinded reading of ileocolonoscopies, and defined by a CDEISm <3 | week 12 | 
| No ulceration |  | week 12 | 
| Clinical remission | defined by Crohn's disease activity index (CDAI)<150 without steroids, anti-Tumor Necrosis Factor (TNF), and surgery | 12 and 48 weeks | 
| Microbiota composition |  | weeks 12 and 48 | 
| lpf positive AIEC bacteria in the stools | Detection (by PCR) | weeks 12 and 48 | 
| Biological remission | defined by haemoglobin level ≥13g/dL and C-Reactive Protein (CRP) serum level ≤5 mg/L and fecal calprotectin <300 mg/L | weeks 4, 8, 12, 24, 36 and 48 | 
| Side effects | adverse events | week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adult, AIEC