Preventing C. difficile recurrence with short-course oral vancomycin during later antibiotics

Secondary Prophylaxis of Recurrent Clostridioides Difficile Infections During Systemic Antibiotics With Vancomycin: A Randomized Controlled Trial

This trial tests whether taking short-course oral vancomycin while you need systemic antibiotics can prevent a recurrence of C. difficile in adults recently treated for CDI.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre (Academic / other)
• Drugs / interventions: bezlotoxumab
• Locations: 1 site (Montreal, Quebec)
• Trial ID: NCT06979609 on ClinicalTrials.gov

What this trial studies

This randomized, placebo-controlled Phase 2/3 trial enrolls adults who had a confirmed C. difficile infection within the past 120 days and who are being re-exposed to systemic antibiotics. Participants are randomized to receive oral vancomycin or placebo twice daily for the duration of the systemic antibiotic course and then once daily for seven days after antibiotics stop. Outcomes include occurrence of recurrent CDI through a follow-up visit at day 56 and weekly electronic questionnaires. The trial is led by the McGill University Health Centre and conducted at their Montreal site.

Who should consider this trial

Good fit: Adults (age ≥18) with a confirmed CDI episode within the previous 120 days who achieved clinical cure after ≥10 days of vancomycin or fidaxomicin and who now require at least one additional day of systemic antibiotics are eligible.

Not a fit: Patients who are not being re-exposed to systemic antibiotics, whose qualifying CDI was more than 120 days earlier, or who did not receive vancomycin or fidaxomicin for the index episode are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, this approach could lower the risk of recurrent C. difficile episodes after patients are re-exposed to systemic antibiotics.

How similar studies have performed: Observational studies and small nonrandomized series have suggested oral vancomycin prophylaxis may reduce recurrence with antibiotic exposure, but high-quality randomized data remain limited.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Patient declared anticipated inability to participate in study follow-up or lack of means for contact in the outpatient setting.

Where this trial is running

Montreal, Quebec

• McGill University Health Centre — Montreal, Quebec, Canada (Recruiting)

Study contacts

• Principal investigator: Todd C. Lee, MD MPH — McGill University Health Centre/Research Institute of the McGill University Health Centre
• Study coordinator: Emily G. McDonald, MD MSc

Conditions Clostridioides Difficile Infection; Clostridioides Difficile Infection Recurrence; Clostridoides Difficile Associated Disease; Clostridioides difficile; Clostridium difficile; Vancomycin; Prophylaxis; C. difficile