Pilot study on the safety and efficacy of ciprofloxacin for prophylactic preventi

描述（由申请人提供）：尽管进行了广泛的医学治疗，但在某些时候，大约70%-80%的患者需要手术切除。然而，绝大多数患者术后会出现疾病复发，严重限制了手术治疗。在这种情况下，细菌菌群起着重要的作用，证明了甲硝唑或奥硝唑术后抗生素治疗的益处，或转移回肠造口患者没有炎症。然而，上述两种抗生素方案都有许多不良事件，限制了这种治疗在日常临床实践中的价值。环丙沙星抑制革兰氏阴性需氧细菌种类，包括肠粘附/侵袭性大肠杆菌菌株，在克罗恩病患者的早期和慢性回肠病变中增加。有限数量的临床数据表明该药物对克罗恩病患者有效。这项探索性的多中心前瞻性、安慰剂对照试验在9个经验丰富的IBD中心进行，将分析40名接受回盲切除术并进行一期吻合的患者（按1:1的比例随机分配）接受环丙沙星与安慰剂治疗6个月的安全性和耐受性。克罗恩病的其他治疗方法将不被允许。本研究的主要目的是评估环丙沙星（500mg bid）与安慰剂片6个月治疗预防克罗恩病患者术后内镜下复发的安全性和耐受性。本研究的次要目的是评估内镜下回肠新末端和回肠结肠吻合处的复发率以及结肠病变的程度。此外，将收集吻合口活检样本和患者DNA及血清学样本，用于后期分析细菌核糖体16S DNA、细菌抗体和DNA多态性（如NOD2、OCTN/1/2、ATG 16L1或IL-23受体）。本研究产生的临床数据将作为研究环丙沙星预防术后内镜下克罗恩病复发有效性的明确临床试验的基础。

DESCRIPTION (provided by applicant): Despite extensive medical treatment, surgical resection is required in approximately 70%-80% of the patients at some time. However, recurrence of the disease after operation occurs in the vast 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 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 Gram negative aerobic bacterial species, including enteroadherent/invasive E. coli strains, which are increased 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 performed at 9 experienced IBD centers 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 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 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 rate of endoscopic recurrence in the neoterminal ileum and at the ileocolonic anastomosis as well as the extent of colonic lesions. Additionally biopsy samples at the anastomotic site and patient DNA and serology samples will be collected for later analysis of bacterial ribosomal 16S DNA, bacterial antibodies and DNA polymorphisms (such as NOD2, OCTN/1/2, ATG 16L1 or IL-23 receptor). 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.