Vancomycin pulse-and-taper versus 10-day fidaxomicin to prevent recurrent C. difficile

Initial Vancomycin Taper for the Prevention of Recurrent Clostridioides Difficile Infection 2: A Randomized Controlled Trial

This trial tests whether a vancomycin pulse-and-taper schedule works as well as a 10-day course of fidaxomicin to prevent recurrence in adults with a first episode or first recurrence of C. difficile.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 500 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre (other)
• Locations: 1 site (Montreal, Quebec)
• Trial ID: NCT07328971 on ClinicalTrials.gov

What this trial studies

Adults with a first episode or first recurrence of Clostridioides difficile infection will be assigned to receive either a vancomycin pulse-and-taper regimen or a 10-day course of fidaxomicin and followed for recurrence through day 56. The primary objective is to show non-inferiority of vancomycin P-T compared with fidaxomicin for preventing recurrent CDI at 56 days. Diagnosis requires a positive C. difficile assay plus compatible symptoms, and local fidaxomicin reimbursement criteria will be applied until dedicated funding is available. This phase 3 interventional comparison is conducted at the McGill University Health Centre in Montreal.

Who should consider this trial

Good fit: Adults (≥18 years) with a confirmed first episode or first recurrence of C. difficile infection who meet the study's diagnostic criteria and local reimbursement eligibility are the ideal candidates.

Not a fit: Patients with multiple prior recurrences (multiply recurrent CDI) or those who do not meet local fidaxomicin reimbursement criteria may not be represented and therefore may not receive direct benefit from this comparison.

Why it matters

Potential benefit: If successful, an inexpensive vancomycin pulse-and-taper could prevent recurrences as effectively as fidaxomicin, improving access and reducing treatment costs.

How similar studies have performed: Network meta-analyses and indirect evidence suggest pulse-and-taper vancomycin may be non-inferior to fidaxomicin, but direct head-to-head randomized evidence is limited.

Eligibility criteria

Inclusion Criteria:

* Inpatient or outpatient adults (≥18 years old) treated at the participating institutions.
* First episode or first recurrence of CDI (i.e., second episode within 56 days) defined by a positive C. difficile assay (including PCR toxin gene detection, toxin enzyme immunoassay, and/or cell cytotoxicity neutralization assay37) and the presence of either ≥3 unformed stools in \<24 hours with a duration \>24 hours, endoscopic/histologic evidence of pseudomembranous colitis, or ileus.
* Because of the prohibitive cost of fidaxomicin, the reimbursement criteria of fidaxomicin by the Régie de l'assurance maladie du Québec will be applied as inclusion criteria until dedicated fidaxomicin funding is available. This includes: either 1) ≥65 years old or immunosuppression, 2) a second episode of C. difficile within 12 weeks of a prior episode of C. difficile, or 3) multiply recurrent CDI (i.e., ≥2 recurrences). When additional funding is obtained, then only inclusion criteria 1 and 2 will be applied.

Exclusion Criteria:

* Planned or current treatment of the present episode of CDI with FMT, intravenous immunoglobulins, or other microbiome therapies (i.e., VOWST or REBYOTA).
* Inability to take medications orally or crushed by tube.
* Prior total colectomy.
* Severe intolerance or allergy to oral vancomycin or fidaxomicin.
* Patient is being admitted to a palliative care ward or is anticipated to die within 3 months of enrollment from another illness.
* Fulminant CDI, defined according to the IDSA definition of CDI with the presence of hypotension, shock, ileus, and/or toxic megacolon. This is because vancomycin is generally preferred at this severity.
* Receipt of more than 72 hours of off-study fidaxomicin or vancomycin CDI therapy for the current episode of CDI.
* Pregnancy or planning to become pregnant during the study period because minimal data on fidaxomicin in pregnancy are available.
* Active breastfeeding because minimal data on fidaxomicin in breastfeeding are available.
* 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: Emily McDonald, MD MSc — McGill University Health Centre/Research Institute of the McGill University Health Centre
• Study coordinator: Connor Prosty, MD

Conditions: Clostridia Difficile Colitis, Clostridoides difficile, Recurrent Clostridioides difficile, C. difficile, Clostridium difficile