STOP-CDI: Efficacy of Fecal Microbiota Transplantation vs Fidaxomicin vs Vancomycin in Treating and Preventing Relapse of Clostridioides Difficile Infection

NCT07120490 | Not Yet Recruiting

• 2 other identifiers: STOP-CDI2022/ABM/03/00047
• Study Type: interventional
• Target: 424
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Clostridioides Difficile Infection; Clostridioides Difficile Infection Recurrence; Fecal Microbiota Transplantation (FMT); Comparative Effectiveness of CDI Treatments; Fidaxomicin; Vancomycin

Keywords

Clostridioides difficile; CDI; Fecal microbiota transplantation; Fidaxomicin; Vancomycin; Recurrent infection

Outcome Measures

Primary Outcomes (1)

• 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.

  12 weeks (90 days) after treatment completion

Secondary Outcomes (7)

• 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

Other Outcomes (1)

• Changes in gut microbiota diversity and composition after FMT

  Baseline, Day 7, Day 14, and Weeks 4, 8, and 12 post-treatment

Study Arms (3)

FECAL MICROBIOTA TRANSPLANTATION (with vancomycin short pretreatment phase)

EXPERIMENTAL

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.

Other: FMT (fecal microbiota transplantation)

ANTIBIOTICS ONLY - FIDAXOMICIN

EXPERIMENTAL

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.

Drug: Fidaxomicin

ANTIBIOTICS ONLY - VANCOMYCIN

EXPERIMENTAL

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.

Drug: Vancomycin (VAN) treatment

Interventions

FMT (fecal microbiota transplantation) OTHER

This 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.

Also known as: Vancomycin short-course pretreatment

FECAL MICROBIOTA TRANSPLANTATION (with vancomycin short pretreatment phase)

Fidaxomicin DRUG

Participants 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.

ANTIBIOTICS ONLY - FIDAXOMICIN

Vancomycin (VAN) treatment DRUG

Participants 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.

ANTIBIOTICS ONLY - VANCOMYCIN

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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,
• 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.

Sponsors & Collaborators

• Medical University of Warsaw: lead
• Human Biome S.A.: collaborator

MeSH Terms

Conditions

Clostridium Infections; Reinfection

Interventions

Fecal Microbiota Transplantation; Fidaxomicin; Vancomycin; Therapeutics

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Recurrence; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biological Therapy; Macrolides; Lactones; Organic Chemicals; Polyketides; Macrocyclic Compounds; Polycyclic Compounds; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Jaroslaw Bilinski, MD PhD, Assoc. Prof.

CONTACT

884 299 668; jaroslaw.bilinski@human-biome.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicenter, randomized, open-label, three-arm study using a parallel assignment model. Eligible participants are randomly allocated in a 2:1:1 ratio to one of three intervention groups: (1) short-course oral vancomycin followed by fecal microbiota transplantation (FMT), (2) fidaxomicin monotherapy, or (3) standard-of-care vancomycin. Each participant remains in their assigned group for the duration of the study and receives only the intervention corresponding to that group. No crossover between arms is planned. The parallel design allows for direct comparison of recurrence rates and treatment outcomes across independent, concurrently treated cohorts. Randomization is stratified by site, and outcome assessors may be blinded for certain exploratory analyses.

Study Record Dates

• First Submitted: July 30, 2025
• First Posted: August 13, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): April 30, 2027
• Last Updated: August 13, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share