Randomised Controlled Trial of Clarithromycin in Active Crohn's Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Remission defined as a CDAI<150 and response defined as a fall in CDAI by more than 70 points from pretreatment level.
研究概览
简要总结
Clarithromycin may be an effective therapy in Crohn's disease. It is a broad spectrum antibiotic. Crohn's disease, the investigators think, is in some way related to bacteria, which reside in the bowel.
Previous studies of different types of antibiotic in Crohn's disease have shown encouraging results. Clarithromycin alters the bacteria in the bowel and gets into cells in the bowel which may contain bacteria. There is some evidence that clarithromycin can stimulate the immune system and improve the function of cells involved in killing bacteria in the bowel.
详细描述
WHAT IS THE PROBLEM TO BE ADDRESSED ?
Lack of effective cure for Crohn's disease.
Effective symptomatic treatment of Crohn's disease can be achieved in approximately 60-80% using corticosteroids [1] with a similar response to enteral or intravenous feeding. The benefit is usually short-term however, with more than 50% relapsing within a year [2] and over 90% of patients with ileocaecal disease eventually requiring at least one surgical operation [3].
The cause of Crohn's disease is unknown but it is commonly believed to be due in some way to bacteria: either as an unusual response to the normal intestinal flora or possibly to a specific infection such as an atypical bacterium. It is typified histologically by the presence of granulomata (in over 75% of cases) and closely resembles intestinal tuberculosis, radiologically and histologically. A search for Mycobacteria has produced conflicting results with one centre claiming that Mycobacterium paratuberculosis DNA can be detected in the majority of cases [4] but with others finding Mycobacterial DNA in only about 10% [5]. Studies have shown that a variety of organisms including normal intestinal bacteria and yeasts can be grown from Crohn's disease mesenteric lymph nodes and that the lymphocytes within these lymph nodes are manufacturing antibodies that are directed against a broad range of bacterial antigens so it is a more widely held view that a wide range of micro-organisms invade the mucosa in Crohn's disease, possibly as a result of a breakdown in the normal mucosal barrier [6].
WHAT IS THE HYPOTHESIS TO BE TESTED?
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with Crohn's disease diagnosed by conventional clinical, radiological and histological criteria.
- •Active Crohn's disease: Crohn's Disease Activity Index (CDAI)> 200 and CRP > 10 mg/l.
- •Patients on 10mg or less of prednisolone or 3mg budesonide.
- •Patients on a stable dose of azathioprine for at least 3 months and on stable dose of 5-ASA preparation for at least one month.
排除标准
- •Patients under 18 or unable to give informed consent.
- •Patients on long term antibiotics for Crohn's disease or other indications
- •Known sensitivity to clarithromycin
- •Pregnant, post partum (<3months) or breast feeding females.
- •Any change to medication for Crohn's disease for previous month.
- •Patients with complications requiring surgery (significant intestinal obstruction, perforation or abscess)
- •CDAI > 450
- •Participation in other trials in the last 3 months.
- •Serious intercurrent infection or other clinically important active disease (including renal and hepatic disease)
- •Patients on cisapride, astemizole or terfenadine (prolonged QT interval and arrhythmias reported with macrolide antibiotics)
研究组 & 干预措施
1 (i)
Clarithromycin S/R 1g od From April 2004, clarithromycin S/R (Klaricid XL) ceased to be available and subsequent patients will receive either standard clarithromycin 500mg bd or placebo tables of identical size, colour and taste
干预措施: Clarithromycin (Drug)
2 (ii)
placebo tablets of identical size, colour and taste
干预措施: Placebo (Drug)
结局指标
主要结局
Remission defined as a CDAI<150 and response defined as a fall in CDAI by more than 70 points from pretreatment level.
时间窗: 2 months
次要结局
- Fall in Van Hees activity index(2 months)
- Improvement in Inflammatory Bowel Disease specific Quality of Life Index(2 months)
- Reduction of serum CRP.(2 months)
- Withdrawal: Rise in CDAI>50 points from baseline(any time during trial)