Crohn Disease, Adherent-invasive E. Coli
Conditions
Keywords
Adult, AIEC
Brief summary
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.
Interventions
DRUGCiprofloxacin
oral Ciprofloxacin 500 mg bis in die (bid) for 12 weeks
DRUGRifaximin
oral Rifaximin 800 mg bid for 12 weeks
a placebo of Ciprofloxacin bid for 12 weeks
a placebo of Rifaximin bid for 12 weeks
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients with Endoscopic Endoscopic Index of Severity (CDEISm)< 6 and a decrease in CDEISm ≥ 3 | week 12 | (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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete endoscopic remission | week 12 | assessed by centralized, anonymous and blinded reading of ileocolonoscopies, and defined by a CDEISm \<3 |
| No ulceration | week 12 | — |
| Clinical remission | 12 and 48 weeks | defined by Crohn's disease activity index (CDAI)\<150 without steroids, anti-Tumor Necrosis Factor (TNF), and surgery |
| Mean variation of CDEISm | week 12 | assessed by centralized, anonymous and blinded reading of ileocolonoscopies |
| lpf positive AIEC bacteria in the stools | weeks 12 and 48 | Detection (by PCR) |
| Biological remission | weeks 4, 8, 12, 24, 36 and 48 | defined by haemoglobin level ≥13g/dL and C-Reactive Protein (CRP) serum level ≤5 mg/L and fecal calprotectin \<300 mg/L |
| Side effects | week 12 | adverse events |
| Microbiota composition | weeks 12 and 48 | — |
Countries
France
Outcome results
None listed