Clinical trial NCT00609973
Conditions: Crohn's Disease
Keywords: Postoperative recurrence, inflammatory bowel disease
Sponsor: University of North Carolina, Chapel Hill
Start date: 2008-05-01; Completion date: 2011-12-01
Enrollment: 33 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Arms: arm 1: Ciprofloxacin 500 mg bid arm 2: Placebo bid
Interventions: intervention 1: Ciprofloxacin intervention 2: Placebo
Intervention descriptions: intervention 1: Ciprofloxacin 500 mg oral bid for 6 months intervention 2: Placebo bid for 6 months

Protocol documents: