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.
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,
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,
Parallel
FMT (fecal microbiota transplantation)
Other interventionThis intervention consists of a two-phase treatment for Clostridioides difficile infection in high-risk adults. First, participants receive a short-course (5 days) of oral vancomycin to reduce C. difficile bacterial load. Following antibiotic pretreatment, fecal microbiota transplantation (FMT) is administered to restore healthy gut microbiota. FMT is delivered primarily via encapsulated microbiota capsules, with alternative routes including colonoscopy, gastroscopy, nasojejunal tube, or rectal enema if capsules are contraindicated. A second FMT dose is given 7 days after the first, either as daily capsules over six days or as a single endoscopic administration. This approach aims to reduce CDI recurrence by combining targeted antibiotic reduction of pathogens with microbiome restoration.
Fidaxomicin
DrugParticipants receive a 10-day course of fidaxomicin administered orally at a dose of 200 mg twice daily. Fidaxomicin is a narrow-spectrum macrocyclic antibiotic specifically targeting Clostridioides difficile with minimal impact on the normal gut microbiota. This monotherapy aims to eradicate C. difficile infection while preserving the intestinal microbiome, thereby reducing the risk of recurrence. No additional interventions are provided during the treatment period. Biological samples are collected before and after treatment to evaluate clinical response, safety, and microbiome changes.
Vancomycin (VAN) treatment
DrugParticipants receive a 10-day course of oral vancomycin at a dose of 125 mg four times daily. Vancomycin is a broad-spectrum glycopeptide antibiotic commonly used as standard-of-care therapy for Clostridioides difficile infection. This monotherapy aims to eradicate C. difficile by reducing bacterial load in the colon. No additional interventions are applied during the treatment period. Biological samples are collected before and after treatment to monitor clinical outcomes, safety, and changes in the gut microbiome.
Recurrence rate of Clostridioides difficile infection (CDI) within 12 weeks after treatment
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.
Initial Clinical Cure Rate
Proportion of patients achieving initial clinical cure, defined as resolution of diarrhea for at least 2 consecutive days during or after completion of standard antibiotic therapy.
Sustained clinical cure rate at 8 weeks post-treatment
Percentage of patients with no recurrence of CDI symptoms and sustained clinical cure (no diarrhea) within 8 weeks (60 days) after completing therapy, confirmed by patient diary and clinical evaluation.
Recurrent CDI Rate at 8 Weeks
Proportion of patients experiencing a recurrence of Clostridioides difficile infection (CDI), defined as a new episode of diarrhea caused by C. difficile within 8 weeks (60 days) after initial clinical cure, confirmed by patient diary and clinical evaluation.
Sustained Clinical Cure Rate (Complete Cure)
Proportion of patients with initial clinical cure and no recurrence of CDI symptoms for 8 weeks (60 days) after completing therapy.
Changes in gut microbiota diversity and composition after FMT
Assessment of the diversity and composition of the intestinal microbiota before and after fecal microbiota transplantation using metagenomic sequencing, to evaluate microbiota restoration.
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Medical University of Warsaw
Lead sponsor
Human Biome S.A.
Collaborator
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