Official Title: “Double-Blind, Placebo Controlled, Randomized, Multicentre, Pilot Study on the Safety and Efficacy of Ciprofloxacin for Prophylactic Prevention of Postoperative Endoscopic Recurrence in Crohn's Disease Patients”

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.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator), Parallel Assignment

Study Primary Completion Date: December 2010

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(s) in this Clinical Trial

• Drug: Ciprofloxacin
  • Ciprofloxacin 500 mg oral bid for 6 months
• Drug: Placebo
  • Placebo bid for 6 months

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: A
  • Ciprofloxacin 500 mg bid
• Placebo Comparator: B
  • Placebo bid

Primary Measures

• Safety and tolerability of ciprofloxacin
  • Time Frame: 6 Months
    Safety Issue?: Yes

Secondary Measures

• Endoscopic recurrence under postoperative treatment with study medication at 6 months
  • Time Frame: 6 months
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: The University of North Carolina, Chapel Hill

Overall Clinical Trial Officials and Contacts

Hans H Herfarth, MD, PhD Principal Investigator University of North Carolina  

Overall Contact: Hans H Herfarth, MD, PhD 919 9666806 hherf@med.unc.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00609973

Study ID Number: Cipro 1.1

ClinicalTrials.gov Identifier: NCT00609973

Health Authority: United States: Food and Drug Administration