A Pilot Randomised Study to Compare Combination Antibiotic Therapy (Ciprofloxacin, Doxycycline and Hydroxychloroquine) With Standard Therapy (Budesonide) in the Treatment of Active Crohn's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 59
- 试验地点
- 1
- 主要终点
- • Remission, defined as Crohn's Disease activity index (CDAI) <150 at 10 weeks without addition of any other medication or treatment for the Crohn's Disease.
研究概览
简要总结
There is growing evidence that Crohn's disease may be caused by replication of bacteria, perhaps particularly E. coli, within macrophages (a specialized sort of white blood cell). Laboratory studies show that a combination of antibiotics that can penetrate macrophages (such as ciprofloxacin and doxycycline) together with the anti-malarial drug hydroxychloroquine (which makes the contents of macrophage vesicles more alkaline and helps them to kill intracellular bacteria) is particularly effective at killing the E. coli within macrophages.
详细描述
Trial Design This is an Open Label Active Study to Compare the Efficacy of 4 weeks Combination Antibiotic Therapy (Oral Ciprofloxacin 500mg bd plus Doxycycline 100mg bd and Hydroxychloroquine 200mg tds) followed by a further 20 weeks continued therapy with Doxycycline 100mg bd and Hydroxychloroquine 200mg tds with Standard Therapy (Oral Budesonide 9mg per day for 8 weeks followed by 6mg per day for 2 weeks and subsequent 3mg per day over a further 2 weeks) in the treatment of adults with Active Crohn's Disease. Patients who fail to respond by 10 weeks will be offered the opportunity to cross over onto the alternative treatment.
Primary endpoint:
- Remission, defined as Crohn's Disease activity index (CDAI) <150 at 10 weeks without addition of any other medication or treatment for the Crohn's Disease.
- Remission, defined as CDAI ≤150 maintained through to 24 weeks
- Remission, defined as CDAI ≤150 maintained through to 52 weeks
Secondary Endpoints:
- Remission defined as CDAI <150 at 4 weeks
- Response defined as a fall in CDAI by >70 points at 4 weeks and 10 weeks
- Markers of cost (days admitted to hospital, days unable to carry out normal daily activities, need for surgery)
- Quality of life at 4 weeks, at 10 weeks, or Early Withdrawal
- Patient global assessment of symptom severity by 10 cm visual analogue score at 4 weeks, at 10 weeks, or Early Withdrawal
- Adverse Events and possible drug-related side effects: nausea, diarrhoea, mood disturbance, sleep disturbance - will all be assessed at each visit
- Fall in Faecal Calprotectin
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
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
- •Patient is willing to participate in the study and has signed the informed consent
- •Patients aged 18 or over with Crohn's disease diagnosed by conventional clinical, radiological and histological criteria.
- •Crohn's disease involving small bowel, colon or both.
- •Active Crohn's disease: Crohn's Disease Activity Index (CDAI)> 220 and CRP>10mg/l.
- •Patients receiving mesalazine (5ASA) must have had a stable dose for at least one month.
- •Patients receiving Azathioprine, or Mercaptopurine (who will be separately stratified) must have had a stable dose for at least 3 months
- •Women of child bearing potential must have a negative urine pregnancy test prior to the start of study medication
排除标准
- •Patients under 18 or unable to give informed consent.
- •Any antibiotic use within the previous 4 weeks
- •Known sensitivity to Ciprofloxacin, Doxycycline, Hydroxychloroquine, or Budesonide
- •Patients with a history of tendon disorders related to Fluoroquinoline administration
- •Any change to immunosuppressive therapy (Azathioprine, or Mercaptopurine) within the previous 3 months.
- •Use of Infliximab or Adalimumab (anti-TNF antibody) or methotrexate within the previous 3 months
- •Concurrent use of systemic corticosteroids in excess of oral prednisolone 5 mgs/day or budesonide 3mg/day)
- •Any change to medication for Crohn's disease in previous 4 weeks.
- •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)
- •Pregnant, post-partum (<3months) or breast feeding females
- •Patients with abnormal visual acuity (that does not correct with glasses) or unexplained visual symptoms
- •Women of Child Bearing Potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period (double barrier methods such as condoms or diaphragms with spermicidal gel or foam), and for up to 4 weeks after the study.
- •Patients who need to continue to receive oral contraceptives (if unwilling to use double barrier methods), oral anticoagulants tricyclic antidepressants, non-steroidal anti-inflammatory drugs (NSAIDs), anticonvulsants, Sucralfate, or Cyclosporine
研究组 & 干预措施
budesonide
Oral Budesonide 9mg per day for 8 weeks followed by 6mg per day for 2 weeks and subsequent 3mg per day over a further 2 weeks
干预措施: Budesonide (Drug)
Ciprofloxacine, doxycycline and hydroxychloroquine
Oral Ciprofloxacin 500mg bd plus Doxycycline 100mg bd and Hydroxychloroquine 200mg tds followed by a further 20 weeks continued therapy with Doxycycline 100mg bd and Hydroxychloroquine 200mg tds
干预措施: Ciprofloxacin (Drug)
Ciprofloxacine, doxycycline and hydroxychloroquine
Oral Ciprofloxacin 500mg bd plus Doxycycline 100mg bd and Hydroxychloroquine 200mg tds followed by a further 20 weeks continued therapy with Doxycycline 100mg bd and Hydroxychloroquine 200mg tds
干预措施: Doxycycline (Drug)
Ciprofloxacine, doxycycline and hydroxychloroquine
Oral Ciprofloxacin 500mg bd plus Doxycycline 100mg bd and Hydroxychloroquine 200mg tds followed by a further 20 weeks continued therapy with Doxycycline 100mg bd and Hydroxychloroquine 200mg tds
干预措施: Hydroxychloroquine (Drug)
结局指标
主要结局
• Remission, defined as Crohn's Disease activity index (CDAI) <150 at 10 weeks without addition of any other medication or treatment for the Crohn's Disease.
时间窗: 10 weeks
Remission
• Remission, defined as CDAI ≤150 maintained through to 24 weeks
时间窗: 24 weeks
prolonged remission
• Remission, defined as CDAI ≤150 maintained through to 52 weeks
时间窗: 52 weeks
prolonged remission
次要结局
- • Patient global assessment of symptom severity by 10 cm visual analogue score at 4 weeks, at 10 weeks, or Early Withdrawal(4 weeks and 10 weeks)
- • Adverse Events and possible drug-related side effects: nausea, diarrhoea, mood disturbance, sleep disturbance - will all be assessed at each visit(throughout 12 month follow-up)
- • Remission defined as CDAI <150 at 4 weeks(4 weeks)
- • Quality of life at 4 weeks, at 10 weeks, or Early Withdrawal(4 weeks and 10 weeks)
- • Markers of cost (days admitted to hospital, days unable to carry out normal daily activities, need for surgery)(52 weeks)
- • Fall in Faecal Calprotectin(4 weeks, 10 weeks, 24 weeks, 52 weeks)
- • Response defined as a fall in CDAI by >70 points at 4 weeks and 10 weeks(4 weeks and 10 weeks)
研究者
Jonathan Michael Rhodes
Professor of Medicine
Royal Liverpool University Hospital