Fecal Microbiota Transplantation for C. Difficile Infection in Solid Organ Transplant Recipients
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 5
- 主要终点
- Compare the Rate of Recurrence of CDI in Solid Organ Transplant Recipients With FMT Compared With Oral Vancomycin
研究概览
简要总结
The objective is to examine the effect of Fecal Microbiota Transplantation (FMT) compared with vancomycin for cure of recurrent C. diff infection (CDI) in solid organ transplant (SOT) recipients in a randomized, controlled clinical trial.
详细描述
Clostridium difficile (C.difficile) is a pathogen of major public health importance, especially in individuals with comorbid conditions such as solid organ transplantation (SOT). The incidence and adverse outcomes of CDI are greatly amplified in the setting of SOT, due to healthcare exposure, antibiotic use and immunosuppression, all of which are ubiquitous in SOT recipients. There are currently no effective treatment options to achieve a sustained cure of recurrent CDI and prevent further recurrence in SOT recipients. A novel approach that has recently gained attention is restoration of the CDI impaired gut microbiome by instillation of stool from a healthy donor into the intestine of a CDI patient. This treatment, called Fecal Microbiota Transplantation (FMT) has been found in non-comparative studies to reduce CDI recurrence dramatically with a reported efficacy of over 95%, however its efficacy in SOT recipients has not been studied and cannot be extrapolated from results in the non-SOT population because SOT recipients are a unique study population due to profound immunosuppression, frequent antibiotic use and frequent opportunities for exposure to CDI all of which markedly, repeatedly and persistently disrupt the gut microbiome. Thus, this critical gap in the field needs to be addressed by a trial of FMT in SOT recipients with CDI.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Is willing to provide written informed consent.
- •Is willing to comply with all study procedures and be available for the duration of the study.
- •Can take oral medication
- •At least 18 years of age.
- •Is a solid organ transplant (SOT) recipient
- •Has had at recurrent C. difficile infection defined as: positive C. difficile testing in stool and diarrhea (three or more loose stools over 24 hours) during the 180 day period following completion of treatment for prior episode
- •History of positive IgG test to cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) for subject or donor
- •Clinical response to 4-14 days of oral antibiotic standard of care treatment for the current episode of CDI. Clinical response is defined as greater than or equal to 25% reduction of diarrhea.
- •Negative urine or serum pregnancy test for women of childbearing potential and agree to use effective form of contraception until 6 weeks post treatment
排除标准
- •Major bowel resection surgery within 90 days of randomization
- •Active intestinal disease (e.g. Crohn's disease, ulcerative colitis)
- •History of total colectomy or bariatric surgery
- •Known or suspected toxic megacolon and/or small bowel ileus
- •Presence of colostomy or ileostomy.
- •Taking concomitant antibiotics within 48 hours of Visit
- •Topical antibiotics, and antibiotics for transplant prophylaxis are permitted
- •Dysphagia; oropharyngeal, S), or patient has evidence of dysphagia when the 'safety test' capsule is administered
- •Currently receiving medication for treatment of acute rejection and/or develop acute rejection prior to administration of FMT
- •Active, Severe Gastroparesis
- •Unwilling to withhold probiotics. Probiotics include supplements, prescriptions, and non-prescriptions. Foods (like yogurt) are not prohibited
- •Neutropenia, ≤ 500 neutrophils/ml [noted in medical records and resulted within 7 days of Visit 1])
- •Symptomatic co-infection with another intestinal pathogen as determined by chart review
- •Concurrent intensive induction chemotherapy, radiation therapy or biological treatment for any active malignancy. Patients on maintenance chemotherapy could be enrolled after consultation with the study Medical Monitor
- •Any severe food allergy, defined as a history of anaphylaxis, systemic urticarial or angioedema attributed to a food and requiring current avoidance precautions
- •Expected life expectancy is less than 6 months
- •Use of investigational drugs, biologics, or devices within 30 days prior to randomization.
- •Women who are pregnant, lactating or planning on becoming pregnant during the study
- •Not suitable for study participation due to other reasons at the discretion of the investigators
研究组 & 干预措施
FMT oral capsules/ oral vancomycin placebo
FMT plus placebo vancomycin
干预措施: FMT oral capsule (Drug)
FMT oral capsules/ oral vancomycin placebo
FMT plus placebo vancomycin
干预措施: Oral Vancomycin placebo (Drug)
Placebo FMT capsules/ Active oral vancomycin
Vancomycin plus FMT enema placebo
干预措施: Oral Vancomycin (Drug)
Placebo FMT capsules/ Active oral vancomycin
Vancomycin plus FMT enema placebo
干预措施: FMT oral placebo (Drug)
结局指标
主要结局
Compare the Rate of Recurrence of CDI in Solid Organ Transplant Recipients With FMT Compared With Oral Vancomycin
时间窗: 60 consecutive days
Recurrence is defined as diarrhea (greater or equal to 3 or more loose stools that take the shape of the collection container in a 24 hr period)
次要结局
- CDI-related Quality of Life (QOL) Compared Using Treatment and Time Interaction as Model Terms While Adjusting for Potential Confounders(Weeks 4, 29 weeks)
- Compare the Change in Gut Microbiota and Evaluate Changes in Microbiota to Assess for Safety of FMT in Patients(up to 30 weeks of study participation)
- Number of Patients Who Experienced Short or Medium Term Adverse Events(Up 30 weeks of study participation)
- Compare the Effects of FMT and Oral Vancomycin on Intestinal Colonization by Multi-drug-resistant Organisms Other Than C. Difficile in SOT Patients(up to 30 weeks of study participation)