Multicenter, Randomized, Open-label, Three-arm Study on the Efficacy of Fecal Microbiota Transplantation vs Fidaxomicin vs Vancomycin in the Treatment and Relapse Prophylaxis of Clostridioides Difficile Infection. STOP-CDI Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 424
- 主要终点
- Recurrence rate of Clostridioides difficile infection (CDI) within 12 weeks after treatment
研究概览
简要总结
The STOP-CDI study is a multicenter, randomized, open-label, three-arm clinical trial comparing the efficacy of fecal microbiota transplantation (FMT) preceded by vancomycin, fidaxomicin monotherapy, and standard-of-care vancomycin in preventing recurrence of Clostridioides difficile infection (CDI) in high-risk adult patients.
CDI is a common healthcare-associated infection with rising incidence and high recurrence rates, particularly in elderly and immunocompromised individuals. While current guidelines recommend fidaxomicin as first-line therapy, its availability and reimbursement remain limited in some healthcare systems. FMT, although effective, is not widely implemented as first-line treatment. This study addresses the need for comparative, real-world data to inform treatment decisions for patients at high risk of severe or recurrent CDI.
Eligible participants include adults aged ≥65 years or younger patients with specific risk factors such as multiple comorbidities, prior CDI episodes, recent hospitalization, use of non-CDI antibiotics, or PPI therapy. Participants will be randomized in a 2:1:1 ratio to one of three treatment arms: (1) vancomycin plus FMT, (2) fidaxomicin, or (3) vancomycin alone. FMT is administered via capsules or, if necessary, alternative endoscopic routes.
The primary endpoint is CDI recurrence within 12 weeks following the initial treatment. Secondary endpoints include clinical cure, safety, and global cure. Exploratory analyses will assess microbiome changes and potential genomic predictors of response. A total of 424 participants will be enrolled across 10 clinical sites in Poland.
The study aims to provide robust, comparative evidence to support clinical guidelines and improve outcomes for patients with CDI, particularly in healthcare systems with limited access to novel therapies.
详细描述
Clostridioides difficile infection (CDI) represents a persistent and growing challenge in modern healthcare, particularly among elderly, hospitalized, and immunocompromised patients. Despite the existence of evidence-based therapeutic guidelines, recurrence rates remain unacceptably high, often leading to cycles of reinfection and retreatment. These recurrent episodes are associated with increased morbidity, reduced quality of life, higher healthcare costs, and, in some cases, life-threatening complications.
While therapies such as fidaxomicin and fecal microbiota transplantation (FMT) have demonstrated superior efficacy in reducing recurrence compared to traditional vancomycin, access to these interventions remains inconsistent. Fidaxomicin is often restricted due to its high cost and limited reimbursement, while FMT-though highly effective-is not yet widely integrated into early-line treatment pathways, largely due to regulatory and logistical barriers, including donor screening, manufacturing infrastructure, and clinician training.
The STOP-CDI study is a multicenter, randomized, open-label, three-arm research experiment designed to directly compare the effectiveness of three therapeutic strategies in preventing recurrent CDI (rCDI) in a real-world, high-risk adult population. The project addresses key gaps identified by international societies such as ESCMID, which emphasize the need for high-quality, head-to-head comparative research in CDI management.
The primary objective is to determine which of the following approaches most effectively prevents CDI recurrence within 12 weeks after treatment completion:
- Short-course oral vancomycin followed by FMT
- Fidaxomicin monotherapy
- Standard-of-care oral vancomycin
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
- •Individuals aged 65 years or older OR individuals aged 18 to 64 years who meet at least one of the following criteria:
- •Presence of at least two comorbid chronic diseases from the groups of cardiovascular diseases, respiratory system diseases, gastrointestinal diseases, autoimmune diseases, cancers, chronic kidney and genitourinary diseases, immunodeficiencies, diabetes, and metabolic diseases,
- •Previous episodes of CDI,
- •Healthcare-associated CDI and/or hospitalization within the last three months,
- •Concurrent use of antibiotics other than CDI treatment after CDI diagnosis,
- •Use of proton pump inhibitors (PPIs) started during or after CDI diagnosis.
- •Documented Clostridioides difficile infection, defined according to ESCMID as:
- •Diagnosis of diarrhea associated with C. difficile defined by:
- •> 3 unformed stools (or >200 ml of unformed stool in patients with stool collection devices) within 24 hours before randomization AND
- •Clinical signs consistent with CDI and microbiological evidence of free C. difficile toxins in an enzyme immunoassay (EIA) without justified evidence of another cause of diarrhea OR
- •Clinical picture consistent with CDI and positive nucleic acid amplification test (NAAT; PCR) preferably with low cycle threshold (Ct) value, or positive toxigenic C. difficile culture OR
- •Pseudomembranous colitis diagnosed during endoscopy or colectomy combined with a positive test for toxigenic C. difficile.
- •No more than 24 hours of prior treatment with vancomycin, metronidazole, or fidaxomicin.
- •Absolute neutrophil count in peripheral blood within 3 days before intervention > 500/µl.
- •Ability to swallow large capsules (using test capsules) or no contraindications for FMT via nasojejunal tube, gastroscopy, colonoscopy, or rectal enema.
- •Provided informed consent for participation in the clinical study.
排除标准
- •Lack of consent to participate in the study or absence of logical contact without possibility of obtaining consent from an authorized person,
- •More than 24 hours of prior treatment with vancomycin, metronidazole, or fidaxomicin,
- •On the day of inclusion (up to 3 days before starting intervention) absolute neutrophil count in blood <500 cells/µl or expected drop to this level within the next 2 days,
- •Diagnosed HIV infection with CD4 lymphocyte count <250 cells/µl,
- •Inability to swallow large capsules (failed test capsule use) or contraindications for FMT via upper or lower gastrointestinal tract, including gastrointestinal perforation, anal atresia, discontinuity of the gastrointestinal tract, and others,
- •Known presence of other pathogens in stool known to cause diarrhea,
- •Life expectancy <3 months,
- •Life-threatening CDI (fulminant at diagnosis - especially with septic shock),
- •Total or subtotal colectomy, ileostomy, or colostomy,
- •Unwillingness or inability to comply with protocol requirements, including any condition (physical, mental, or social) that may affect the participant's ability to adhere to the protocol.
研究组 & 干预措施
FECAL MICROBIOTA TRANSPLANTATION (with vancomycin short pretreatment phase)
Participants receive oral vancomycin (125 mg QID) for 5 days (extendable to 10 if needed), followed by FMT. On Day 6, bowel cleansing is performed (macrogol-based), and biological samples (stool, blood, urine, saliva) are collected. On Day 7, FMT is administered via preferred oral capsules or, if necessary, colonoscopy, gastroscopy, NJ tube, or rectal enema. A second FMT is given either as daily capsules on Days 9-14 or as a single dose via other routes on Day 14. Dosing: 6 jars of capsules or 200 mL suspension (≥35 kg); half for <35 kg. Supportive measures include antiemetics and fasting. Oral non-antibiotic medications continue. Post-FMT samples are collected for follow-up analyses.
干预措施: FMT (fecal microbiota transplantation) (Other)
ANTIBIOTICS ONLY - FIDAXOMICIN
Participants receive fidaxomicin 200 mg twice daily for 10 days. Biological samples (stool, blood, urine, saliva) are collected at baseline (before first antibiotic dose) for microbiome and safety analyses (PRE ATB). No additional interventions are applied. The antibiotic eradication phase ends on Day 10, after which the participant enters the follow-up phase. Post-treatment biological samples are collected (POST ATB) to assess treatment response, recurrence risk, and microbiota changes.
干预措施: Fidaxomicin (Drug)
ANTIBIOTICS ONLY - VANCOMYCIN
Participants receive vancomycin 125 mg four times daily for 10 days. Biological samples (stool, blood, urine, saliva) are collected prior to the first dose (PRE ATB) for safety and exploratory analyses. No additional therapies are administered. The eradication procedure is completed on Day 10, followed by a post-treatment sampling phase (POST ATB) for assessment of recurrence, clinical response, and microbiome status.
干预措施: Vancomycin (VAN) treatment (Drug)
结局指标
主要结局
Recurrence rate of Clostridioides difficile infection (CDI) within 12 weeks after treatment
时间窗: 12 weeks (90 days) after treatment completion
Proportion of patients experiencing a new episode of CDI, defined as recurrent diarrhea with confirmed C. difficile infection, within 12 weeks (90 days) after initial clinical cure following intervention.
次要结局
- Initial Clinical Cure Rate(Up to 10 days from treatment initiation)
- Sustained clinical cure rate at 8 weeks post-treatment(8 weeks (60 days) after treatment completion)
- Recurrent CDI Rate at 8 Weeks(8 weeks (60 days) after completion of therapy)
- Sustained Clinical Cure Rate (Complete Cure)(8 weeks (60 days) after treatment completion)
- Sustained Clinical Cure Rate (Durable Cure)(12 weeks (90 days) after treatment completion)
- Rate of Treatment-Resistant CDI(Up to 10 days from treatment initia)
- Incidence of Adverse Events(Up to 90 days after treatment)