Lyophilized Fecal Microbiome Transfer for Primary Clostridioides Difficile Infection (DONATE Study): a Multicenter Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 196
- 试验地点
- 6
- 主要终点
- CDI recurrence
研究概览
简要总结
The goal of this clinical trial is to test whether lyophilized fecal microbime transfer - a dried extract of bacteria from the stool of healthy donors - is better than antibiotic therapy only for treating primary clostridioides difficile infection (CDI) in adult participants.
The main question it aims to answer is whether lyophilized fecal microbiome transfer lowers the number of episodes of CDI compared to antibiotic therapy.
Participants will be assigned to one of two groups:
- In the intervention group participants will be given vancomycin by mouth for five days followed by 5 days of capsules of lyophilized fecal microbiome to swallow, up until day 10.
- In the control group participants will be given vancomycin by mouth for ten days.
- All participants will be asked to arrive for two follow-up visits and to fill out questionnaires. In addition, all participants will be asked to give stool samples before antibiotic therapy and on the two follow-up visits.
Researchers will compare the intervention group and the control group to see if there is a difference in symptoms degree after ten days and in recurrence of the infection after two months. They will also compare side effects, the total use of antibiotics and the change in the composition of bacteria in the stool, namely the presence of bacteria that are resistant to many drugs.
详细描述
This is a multicenter, transnational randomized controlled trial comparing a short course of vancomycin therapy followed by oral lyophilized fecal microbiome transfer (Lyo-FMT) capsules (intervention group) with standard vancomycin monotherapy (control group), for adults with primary Clostridioides difficile infection (pCDI).
The target population will be adult patients with non-fulminant pCDI in the community/hospital according to the setting at the recruiting center. pCDI will be defined as the patient's first event of CDI in the last 6 months presenting with a new-onset diarrhea (≥3 unformed bowel movements per day for more than 24 hours) and laboratory detection of toxigenic C. difficile in feces. A positive C. difficile stool sample will be defined per study center according to international guidelines, with an obligatory positive toxin test to assure the presence of an active toxigenic CD strain. Both non-severe and severe patients will be included.
Consenting patients will be randomly assigned to one of two treatment modalities: vancomycin followed by oral lyophilized FMT capsules (intervention group) or vancomycin monotherapy group.
- Lyo-FMT group (intervention group) - vancomycin will be given orally in 125 mg capsules/solution 4 times daily for a total of 5 days (day 1 - initiation of antibiotic therapy by the clinical team), followed by a loading dose of oral lyophilized FMT capsules on day 6 (15 capsules). On days 7-10, patients will receive 10 Lyo-FMT capsules per day. A total of 55 capsules, derived from ~30-40g of the original material, will be administered throughout 5 days. Prior to each FMT administration, patients will be asked to fast for 8 hours. Bowel preparation or proton pump inhibitor use will not be required per protocol. The loading dose will be administered under medical supervision, while further dosing can be administered at the patient's home/institute, after training and guidance.
- Antibiotic monotherapy group (control group) - vancomycin will be given orally in 125 mg capsules/solution 4 times daily for a total of 10 days (day 1 - initiation of therapy by the clinical team, not from randomization).
If symptoms persist on day 10 from the initiation of therapy, further treatment will be given according to study group allocation. In the Lyo-FMT group, FMT will be repeated in the form of 15 FMT capsules per course as clinically indicated. If no resolution of symptoms will be documented after 2 days of FMT, the same FMT course (15 capsules) will be repeated, up to 3 times. For patients in the antibiotic monotherapy group, an extension of the vancomycin treatment with the same doses will be given for 7 more days. Laboratory testing for the presence of C. difficile will not be required for the administration of repeated treatment, but will be annotated if performed. If symptoms will persist beyond day 18 of the study in both groups (8 days after the end of first treatment), we will allow treatment according to clinical judgement at the local study center. Patients will be free to decide if they want to stop their participation in the study at all times. Persistent symptoms beyond day 20 of the study will be considered as a clinical failure for the purposes of secondary outcome analysis. At any point, if there is a deterioration of the patient towards fulminant disease, clinical judgement will prevail as per protocol for fulminant cases.
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
- Single (Outcomes Assessor)
盲法说明
The primary outcome will be assessed by an observer blinded to study group assignment
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
- •Consenting adults ≥18 years old with non-fulminant primary CDI.
- •Both non-severe and severe patients will be included.
- •Primary CDI (pCDI) will be defined as the patient's first event of CDI in the past 6 months: New-onset diarrhea (≥3 unformed bowel movements (UBM) per day for more than 24 hours) and laboratory detection of toxigenic C. difficile in feces.
- •A positive CD stool sample will be defined per study center according to international guidelines, with an obligatory positive toxin test to assure the presence of an active toxigenic CD strain.
排除标准
- •Patients who cannot provide informed consent and do not have a legal guardian;
- •History of CDI 6 months prior to screening
- •Known presence of other stool pathogens known to cause diarrhea;
- •Patients who cannot swallow;
- •Background diagnosis of inflammatory bowel disease, irritable bowel syndrome (IBS), or any other chronic diarrheal disorder;
- •Active gastrointestinal graft versus host disease (GVHD);
- •Neutropenia <500/ml3;
- •Food allergy leading to anaphylaxis;
- •Prior total colectomy or the presence of a small intestinal stoma;
- •Perforated intestine or intestinal fistula or major abdominal surgery in the last 30 days;
- •Fulminant or life-threatening CDI defined as the occurrence of ileus, septic shock or toxic megacolon. Signs of fulminant disease are: white blood cell count >30,000 cells/mL; temperature >40°C; evidence of hypotension [systolic blood pressure <90 mmHg], peritoneal signs, and significant dehydration;
- •Early fulminant CDI (ICU patients) defined as patients showing progression despite treatment with a sequential organ failure assessment score (SOFA score) ≥ 4 due to CDI (13) at day 2 of treatment (prior to randomization);
- •Patients who receive systemic antibiotics due to other reasons which cannot be stopped until 1 day prior to randomization (day 2 of antibiotic therapy);
- •Patients that were not recruited to the study by day 4 of CDI therapy will be excluded from participation;
- •Patients with <3 months life expectancy;
- •Inability or unwillingness to comply with the study protocol, including ingesting capsules, and providing blood or stool samples as scheduled;
- •Participation in another interventional study;
- •In the opinion of the investigator, inappropriateness for the trial (eg, patients with known hypersensitivity to vancomycin);
- •Pregnancy and breastfeeding.
研究组 & 干预措施
Lyophilized fecal microbiome transfer (Lyo-FMT)
Vancomycin will be given orally in 125 mg capsules/solution 4 times daily for a total of 5 days (day 1 - initiation of therapy by the clinical team), followed by a loading dose of oral Lyo-FMT capsules on day 6 (15 capsules). On days 7-10, patients will receive 10 Lyo-FMT capsules per day. A total of 55 capsules, derived from ~30-40g of the original material, will be administered throughout 5 days. Prior to each Lyo-FMT administration, patients will be asked to fast for 8 hours. Bowel preparation or proton pump inhibitor use will not be required per protocol. The loading dose will be administered under medical supervision, while further dosing can be administered at the patient's home/institute, after training and guidance
干预措施: Lyophilized fecal microbiome transfer (Combination Product)
Vancomycin monotherapy
Vancomycin will be given orally in 125 mg capsules/solution 4 times daily for a total of 10 days (day 1 - initiation of therapy by the clinical team, not from randomization).
干预措施: Vancomycin (Drug)
结局指标
主要结局
CDI recurrence
时间窗: 8 weeks
The re-appearance of CDI symptoms (at least 3 unformed bowel movements per day for at least 2 days) with positive CD stool test more than 3 days after the resolution of symptoms and requiring anti-CDI treatment
次要结局
- CDI recurrence in patients who achieved clinical cure(8 weeks)
- Sustained clinical response(8 weeks)
- Clinical cure(10 days)
- Serious adverse events(8 weeks)
- Patient reported outcomes (PROs) and preferences(At baseline and 8 weeks)
- Patient preference for treatment(At baseline and week 8)
研究者
Milena Pitashny, MD
Director of Clinical and Research Microbiome Center
Rambam Health Care Campus