Ciprofloxacin for the Prevention of Postoperative Endoscopic Recurrence in Crohn's Disease
Condition: Crohn's Disease
MeSH terms: Crohn Disease; Recurrence
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      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. In this setting the
      bacterial flora plays an important role as demonstrated by the benefit of a postoperative
      antibiotic therapy with either metronidazole or ornidazole or the absence of inflammation in
      patients with diverting ileostomy. However, both aforementioned antibiotic regimens have
      numerous adverse events limiting the value of this therapy in daily clinical practice.
      Ciprofloxacin suppresses the gram negative aerobic bacterial flora including E.coli strains,
      which can be found in early and chronic ileal lesions of Crohn's disease patients. A limited
      number of clinical data suggest efficacy of this drug in patients with established Crohn's
      disease. This exploratory multicenter prospective, placebo-controlled trial will 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) with primary anastomosis. No other treatments for Crohn's disease will be
      permitted. The primary objective of this study is to assess the safety and tolerability of a
      6 months therapy of ciprofloxacin (500 mg bid) vs. placebo tablets for prevention of
      endoscopic recurrence in postoperative Crohn's disease patients. The secondary objectives of
      this study are to evaluate the endoscopic recurrence in the neoterminal ileum and at the
      ileocolonic anastomosis as well as the extent of colonic lesions. Additionally bioptic
      samples at the anastomotic site and patient DNA samples will be collected for later analysis
      of bacterial ribosomal 19S RNA and DNA polymorphisms (such as NOD2 or IL-23). The clinical
      data generated by this study will serve as a basis for a definitive clinical trial
      investigating the effectiveness of ciprofloxacin in the prevention of endoscopic recurrence
      in postoperative Crohn's disease.
    

Intervention name(s): Ciprofloxacin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Ciprofloxacin 500 mg oral bid for 6 months; Placebo bid for 6 months
Intervention MeSH terms: Ciprofloxacin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: Postoperative recurrence, inflammatory bowel disease