Rectal Bacteriotherapy, Fecal Microbiota Transplantation or Oral Vancomycin Treatment of Recurrent Clostridium Difficile Infections
试验速览
- 阶段
- 3 期
- 入组人数
- 450
- 试验地点
- 2
- 主要终点
- Clinical cure of recurrent Clostridium difficile infection defined as patient-reported abscence of Clostridium difficile infection 90 days after treatment.
研究概览
简要总结
The purpose of the study is to investigate if treatment with fecal microbiota transplantation or rectal bacteriotherapy is superior to standard vancomycin in patients with recurrent Clostridium Difficile infections.
详细描述
Clostridium difficile infection (CDI) is the most common nosocomial infection in the western world. CDI is associated with high morbidity and mortality and is a great burden for the health care system leading Center of Disease Control and Prevention (CDC) to identify it as one of three most important/urgent threats to public health.
Despite antimicrobial treatment of CDI, 20% of the patients have recurrence of CDI. Due to a dysbiosis in the gut microbiota the antimicrobial treatment seems to be less effective.
Fecal microbiota transplantation (FMT) is an alternative treatment for recurrent CDI. Studies have shown a cure rate up to 90% in patients with recurrent CDI. One alternative to FMT is rectal bacteriotherapy (RBT) which is a standardized bacterial culture made in the laboratory consisting of 12 different bacteria. RBT has never been investigated in a clinical trial.
The project is a randomized controlled trial including 450 patients with recurrent CDI will be, after accepting participation, allocated to receive vancomycin alone or vancomycin followed by either FMT or RBT. The patients will be followed up for 180 days. Cure is defined as resolution of CDI symptoms 90 days after treatment.
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
- 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
- •Age ≥ 18 years
- •Verified recurrent CDI with symptoms of CDI and microbiological verification (PCR).
- •Previously treated for CDI with at least 10 days of vancomycin or metronidazole.
- •Be able to read and understand Danish.
排除标准
- •Life expectancy < 3 months.
- •Allergy toward vancomycin
- •Other infection in the GI tract with clinical symptoms similar to CDI.
- •Other illness in the GI tract with clinical symptoms similar to CDI.
- •Use of antibiotics for more than 14 days treating other infections
- •Planning pregnancy, pregnancy or breast feeding.
- •Severe immune suppression which makes FMT/RBT relatively contraindicated
研究组 & 干预措施
Vancomycin
Oral vancomycin according to number of recurrences (Danish guidelines):
First recurrence: Capsule vancomycin 125 mg x 4 p.o. times daily for 14 days
≥2 recurrences:
- capsule vancomycin 125 mg x 4 times daily p.o. for 14 days followed by
- capsule vancomycin 125 mg x 2 times daily p.o. for 7 days followed by
- capsule vancomycin 125 mg x 1 times daily p.o. for 7 days followed by
- capsule vancomycin 125 mg x 1 p.o. every second day for 7 days followed by
- capsule vancomycin 125 mg x 1 p.o. every third day for 14 days
干预措施: Vancomycin (Drug)
Vancomycin + fecal microbiota transplantation
Capsule vancomycin 125 mg x 4 times daily p.o. for 7-14 days followed by Fecal Microbiota Transplantation with 200 ml fecal suspension administrated with a rectal catheter.
干预措施: Vancomycin (Drug)
Vancomycin + fecal microbiota transplantation
Capsule vancomycin 125 mg x 4 times daily p.o. for 7-14 days followed by Fecal Microbiota Transplantation with 200 ml fecal suspension administrated with a rectal catheter.
干预措施: Fecal microbiota transplantation (Drug)
Vancomycin + rectal bacteriotherapy
Capsule vancomycin 125 mg x 4 times daily p.o. for 7-14 days followed by Rectal bacteriotherapy with 200 ml suspension of a fixed mixture of bacterial strains administrated with a rectal catheter.
干预措施: Vancomycin (Drug)
Vancomycin + rectal bacteriotherapy
Capsule vancomycin 125 mg x 4 times daily p.o. for 7-14 days followed by Rectal bacteriotherapy with 200 ml suspension of a fixed mixture of bacterial strains administrated with a rectal catheter.
干预措施: Rectal bacteriotherapy (Drug)
结局指标
主要结局
Clinical cure of recurrent Clostridium difficile infection defined as patient-reported abscence of Clostridium difficile infection 90 days after treatment.
时间窗: 90 days
Clinical cure defined as patient-reported abscence of Clostridium difficile infection 90 days after treatment. The investigator will call the patient by telephone and fill out af digital questionnaire.
次要结局
- Compare numbers of patients with clinical cure after study treatment divided into two groups depending on numbers of recurrences of CDI.(90 days after ended treatment)
- Effect of the treatment depending on the CD strain - i.e. toxin B CDI cases, toxin B plus binary toxin CDI cases and CD027 CDI cases.(90 days after ended treatment)
- Effect of the treatment depending on the patients serum-level of antibodies towards toxin A and B at the time of inclusion.(90 days after ended treatment)
- Side effects in the three treatment arms(14 days after ended treatment)
- Characterisation of the gut microbiota before and after treatment with FMT/RBT in conjunction with characterisation of the donor's microbiota or the RBT bacterial mix.(180 days after ended treatment)
- Other antibiotic treatments associated with new recurrences of CDI(Within 180 days after ended treatment)
- Evaluation of the composition of bile acids before and after treatment with FMT/RBT.(90 days after ended treatment)
- Characterisation of the CD strains by whole genome sequencing(90 days after ended treatment)
- Identification of age as a risk factor for treatment success/failure(90 days after ended treatment)
- Identifying if Charlson comorbidity index is associated to treatment success/failure.(90 days after ended treatment)
- CDI-associated hospital admission and hospital admission of other causes in the follow-up period(180 days after ended treatment)
- CDI-associated mortality and all-cause mortality(30, 90 and 180 days after ended treatment)
- Days with diarrhea(1, 4, 8 and 12 days after ended treatment)
- Early or late recurrence of CDI after the end of treatment defined as recurrence of symptoms of CDI and a positive stool sample with Clostridium difficile (PCR).(30 and 180 days after ended treatment)
- CDI-associated hospital outpatient contact and hospital outpatient contact of other causes in the follow-up period(180 days after ended treatment)
研究者
Andreas Munk Petersen
MD, PhD
Hvidovre University Hospital