Secondary Prevention of Clostridioides Difficile Using Vancomycin

NCT06979609 | Recruiting Phase 2 DMC

• 1 other identifier: 2025-11089
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Re-exposure to systemic antibiotics (i.e., antibiotics absorbed into the bloodstream) is common after a Clostridioides difficile infection (CDI) and is the strongest risk factor for a recurrent episode. Oral vancomycin to prevent a recurrence during antibiotic re-exposure may reduce this risk but the data supporting this practice are limited. The aim of this trial is: 1\) Does oral vancomycin prophylaxis prevent CDI recurrences in patients with recent CDI (within 120 days) and who are re-exposed to systemic antibiotics? The trial will compare oral vancomycin to placebo. Participants will:

• Take the study drug (either vancomycin or placebo) twice daily for the duration of systemic antibiotics plus once daily for 7 days after completion of systemic antibiotics.
• Attend an in-person follow-up at day 56
• Respond to weekly electronic questionnaires

Conditions

Clostridioides Difficile Infection; Clostridioides Difficile Infection Recurrence; Clostridoides Difficile Associated Disease

Keywords

Clostridioides difficile; Clostridium difficile; Vancomycin; Prophylaxis; C. difficile; Recurrence; CDI

Outcome Measures

Primary Outcomes (1)

• CDI Recurrence

  Patients reporting diarrhea will be brought in for an in-person appointment that is standard of care for patients with potential rCDI and investigated as appropriate clinically without unblinding. Additionally, patients and/or their proxy will be instructed to contact the study team if they believe they are having a recurrence between contacts. Patients will be able to come be assessed for potential recurrence by infectious diseases physicians at each site (who may or may not be a part of the study) or could see their usual doctors. Recurrence will be assessed by clinical record review (chart, laboratory, pharmacy records) and any direct patient interview. CDI recurrence will be defined by 1) three or more unformed stools in a 24-hour period, 2) a positive PCR for toxin gene or and/or detection of toxin by enzyme immunoassay or cell cytotoxicity neutralization assay, and 3) administration of CDI treatment. This is similar to the definition used in the NEJM fidaxomicin trial.

  56 Days

Secondary Outcomes (4)

• Late CDI Recurrence

  90 Days

• All-Cause Mortality

  90 Days

• Discontinuation of the Study Drug Due to Adverse Event

  56 Days

• Emergency Room Visits or Hospital Admissions

  90 Days

Study Arms (2)

Oral Vancomycin Prophylaxis

EXPERIMENTAL

Vancomycin 125mg PO BID for the duration of antibiotic re-exposure + 125mg PO QD for 7 days

Drug: Oral Vancomycin Prophylaxis

Placebo

PLACEBO COMPARATOR

2 capsules PO BID for the duration of antibiotic re-exposure + 1 capsule PO QD for 7 days

Drug: Placebo

Interventions

Oral Vancomycin Prophylaxis DRUG

125mg PO BID for the duration of antibiotic re-exposure + 125mg PO QD for 7 days

Oral Vancomycin Prophylaxis

Placebo DRUG

2 capsules PO BID for the duration of antibiotic re-exposure + 1 capsule PO QD x 7 days

Placebo

Eligibility Criteria

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

You may qualify if:

• Inpatient or outpatient adults (≥18 years old) treated at the participating institutions.
• An episode of CDI within the preceding 120 days (rationale in 2.4), diagnosed by both a positive C. difficile assay (including PCR toxin gene detection47, toxin enzyme immunoassay, and/or cell cytotoxicity neutralization assay29) and the presence of either ≥3 unformed stools in \<24 hours with a duration \>24 hours, endoscopic/histologic evidence of pseudomembranous colitis, or ileus29.
• Treatment of the qualifying CDI episode with vancomycin or fidaxomicin for ≥10 days, clinical cure (≤3 unformed stool per 24 hours in ≥2 days10) by the conclusion of therapy, and ≥1 day has elapsed since cessation of CDI treatment.
• Receipt of ≤3 days of at least one oral or intravenous systemic antibiotic for the treatment of an intercurrent confirmed or suspected bacterial infection, for which therapy is planned for at least one additional consecutive day in duration.

You may not qualify if:

• Treatment of the qualifying episode of CDI with metronidazole monotherapy or intravenous immunoglobulins.
• Planned treatment with or treatment of the qualifying episode of CDI with fecal microbiota transplantation (FMT), bezlotoxumab, VOWST, or REBYOTA.
• Inability to take medications orally or crushed by nasogastric tube.
• Prior total colectomy.
• Severe intolerance or allergy to oral vancomycin.
• Lack of achievement of clinical cure during the treatment of the qualifying CDI episode
• Ongoing or \<1 day since receiving CDI treatment or ongoing or \<1 days since receipt of CDI-active antibiotics, including oral vancomycin, oral or intravenous metronidazole, or fidaxomicin.
• The qualifying antibiotic is solely for prophylaxis (e.g., once daily trimethoprim sulfamethoxazole) or the patient is anticipated to require systemic antibiotics for \>4 weeks (e.g., lifelong suppressive therapy or for the treatment of left-sided endocarditis or a deep-seated abscess).
• Patients on ongoing systemic antibiotics since the completion of treatment for the qualifying episode of CDI that have not been interrupted by at least one day.
• Patients admitted to a palliative care ward or is anticipated to die within 3 months of enrollment from another illness.
• The qualifying antibiotic is non-systemic or is not considered a significant risk factor for CDI including: topical antibiotics, azithromycin, clarithromycin, nitrofurantoin, intravenous vancomycin, minocycline, tetracycline, doxycycline, and oral fosfomycin.
• Prior enrollment in this trial.
• Inability to consent without a healthcare proxy.
• Lack of health insurance.
• Anticipated transfer to a site not involved in this trial or to a palliative care ward.

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

Study Sites (1)

McGill University Health Centre

Montreal, Quebec, H4A3J1, Canada

RECRUITING

Related Publications (19)

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MeSH Terms

Conditions

Clostridium Infections; Recurrence

Condition Hierarchy (Ancestors)

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

Study Officials

• Todd C. Lee, MD MPH

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

• Connor J. Prosty, MD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emily G. McDonald, MD MSc

CONTACT

514-934-1934; cdi@idtrials.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of General Internal Medicine

Study Record Dates

• First Submitted: May 13, 2025
• First Posted: May 20, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2029
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)