Ciprofloxacin for the Prevention of Postoperative Endoscopic Recurrence in Crohn's Disease
Condition: Crohn's Disease
MeSH terms: Crohn Disease; Recurrence
Intervention: Ciprofloxacin; Placebo
Intervention description: Ciprofloxacin 500 mg oral bid for 6 months; Placebo bid for 6 months
Intervention MeSH terms: Ciprofloxacin
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Postoperative recurrence, inflammatory bowel disease

Summary:

      Despite extensive medical treatment, surgical resection is required in approximately 70% of
      the patients at some time. However, recurrence of the disease after operation occurs in the
      majority of patients and is a serious limitation of surgical management. Therapeutic options
      to maintain postoperative clinical remission are urgently needed. Several drugs including
      mesalazine, antibiotics (metronidazole, ornidazole) and azathioprine or 6-mercaptopurine have
      been studied in the past. But the efficacy is very limited (mesalazine), overshadowed by
      intolerability during long-term therapy (metronidazole, ornidazole) or inconclusive
      (azathioprine or 6-mercaptopurine). Research demonstrating the absence of inflammation in
      patients with diverting ileostomy and the clinical benefit of a postoperative antibiotic
      therapy using metronidazole or ornidazole implicates a role of the resident bacterial flora
      in the postoperative relapse. Ciprofloxacin has a broad antibacterial spectrum. More
      interestingly it also suppresses E. coli strains, which can be found in high numbers in early
      and chronic ileal lesions of Crohn's disease patients Ciprofloxacin has demonstrated
      beneficial effects in the therapy of inflammatory bowel diseases, but the available data of
      the effectiveness of ciprofloxacin allow only a very limited judgement of the safety and
      tolerability of a 6 months therapy of ciprofloxacin. Therefore an exploratory multicenter
      prospective, placebo-controlled trial is planned to analyze the safety and tolerability of a
      6 months therapy with ciprofloxacin compared to placebo in 40 patients (randomly assigned in
      a 1:1 ratio) undergoing ileocecal resection (or resection of parts of the colon). If this
      therapeutic regimen demonstrates tolerability, a second larger study improving the
      superiority of ciprofloxacin versus placebo can be initiated.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed informed consent.

          -  Man or woman between 18 and 70 years of age.

          -  Diagnosis of Crohn's disease confirmed during index surgery.

          -  Detailed assessment of disease localization by colonoscopy, small bowel radiography,
             and/or other appropriate methods (e.g., MRI, CT) within 6 months prior inclusion into
             the study.

          -  Resection for ileal or ileo-colonic Crohn's disease with ileo-colonic anastomosis
             (i.e., without grossly visible disease at the resection margins); neoterminal ileum
             should be assessable by endoscopy.

          -  Ability to start oral nutrition and medication intake within 14 days after index
             surgery.

          -  Negative pregnancy test at screening visit in females of childbearing potential.

          -  Use of appropriate contraceptive methods for females of childbearing potential and
             males with procreative capacity during treatment.

        Exclusion Criteria:

          -  Short bowel syndrome.

          -  Previous long term therapy with ciprofloxacin (> 6 weeks prior before surgery)

          -  Patients in whom any visible lesions at the anastomosis were left after index surgery.

          -  Serious secondary illnesses of an acute or chronic nature, which in the opinion of the
             Investigator renders the patient unsuitable for inclusion into the study.

          -  Dementia

          -  Uncontrolled Diabetes Type I type II

          -  Known drug abuse

          -  Known parasitic disease of the digestive system

          -  Active replicating Hepatitis B or Hepatitis C

          -  HIV-infection

          -  Seizure disorder

          -  Serum creatinine levels exceeding 1.5 mg/dL or 130 μmol/L.

          -  Presence of an ileal or colonic stoma.

          -  Known previous or concurrent malignancy (other than that considered surgically cured,
             with no evidence for recurrence for 5 years).

          -  Application of non-steroidal anti-inflammatory drugs as long term treatment.

          -  Known intolerance/hypersensitivity to ciprofloxacin or other quinolones or drugs of
             similar chemical structure or pharmacological profile.

          -  Chronic use of CYP1A2 substrates (aminophylline, fluvoxamine, mexiletine, mirtazapine,
             ropinirole, tizanidine, trifluoperazine)

          -  Well-founded doubt about the patient's cooperation.

          -  Existing pregnancy, lactation, or intended pregnancy or impregnation within the next 3
             months.

          -  Non-use of appropriate contraceptives in females of childbearing potential (e.g.
             condoms, intrauterine device [IUD], hormonal contraception for females, or a means of
             contraception for a particular patient considered adequate by the responsible
             investigator) during treatment.

          -  Participation in another clinical trial within the last 30 days, simultaneous
             participation in another clinical trial, or previous participation in this trial.