Vancomycin Taper to Prevent Recurrent Clostridioides Difficile

NCT07328971 | Recruiting Phase 3 DMC

• 1 other identifier: 2026-12121
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Indirect evidence from network meta-analyses of randomized controlled trials (RCTs) suggest that a pulse and taper (P-T) of vancomycin may be non-inferior to 10-days of fidaxomicin for the prevention of recurrent Clostridioides difficile infections (rCDI). The aim of this trial is: 1\) For first episodes and first recurrences of CDI, to test whether a vancomycin P-T is non-inferior to 10-days of fidaxomicin for the prevention of rCDI at 56 days

Conditions

Clostridia Difficile Colitis

Keywords

Clostridoides difficile; Recurrent Clostridioides difficile; C. difficile; Clostridium difficile

Outcome Measures

Primary Outcomes (1)

• CDI Recurrence

  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. To avoid missing severe recurrences for cases of ileus, toxic megacolon, or pseudomembranous colitis on colonoscopy the test result and administration of treatment will fulfill criteria for a recurrence in the absence of three or more unformed stools.

  56 days

Secondary Outcomes (5)

• All-Cause Mortality

  56 days

• All-Cause Mortality

  120 days

• Discontinuation of study drug due to adverse events

  56 days

• ER Visit or Hospital (Re)Admission

  56 days

• ER Visit or Hospital (Re)Admission

  120 days

Other Outcomes (2)

• Quality of Life: Clostridioides difficile Health-related Quality of Life Questionnaire (Cdiff32)

  56 days

• Quality of life: EuroQol 5 Dimensions 5 Levels (EQ-5D-5L)

  56 days

Study Arms (2)

Fidaxomicin

ACTIVE COMPARATOR

Fidaxomicin 200mg PO BID x 10 days

Drug: Fidaxomicin

Vancomycin T-P

EXPERIMENTAL

Vancomycin 125mg PO QID x2 weeks, then 125mg PO BID x2 weeks, then 125mg PO daily x2 weeks

Drug: Vancomycin capsule

Interventions

Vancomycin capsule DRUG

Vancomycin 125mg PO QID x2 weeks, then 125mg PO BID x2 weeks, then 125mg PO daily x2 weeks

Vancomycin T-P

Fidaxomicin DRUG

Fidaxomicin 200mg PO BID x 10 days

Fidaxomicin

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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

McGill University Health Centre

Montreal, Quebec, H4A0B1, Canada

RECRUITING

Related Publications (3)

• Louie TJ, Miller MA, Mullane KM, Weiss K, Lentnek A, Golan Y, Gorbach S, Sears P, Shue YK; OPT-80-003 Clinical Study Group. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011 Feb 3;364(5):422-31. doi: 10.1056/NEJMoa0910812.

  PMID: 21288078 BACKGROUND

• Johnson S, Lavergne V, Skinner AM, Gonzales-Luna AJ, Garey KW, Kelly CP, Wilcox MH. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis. 2021 Sep 7;73(5):e1029-e1044. doi: 10.1093/cid/ciab549.

  PMID: 34164674 BACKGROUND

• McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V, Shaklee Sammons J, Sandora TJ, Wilcox MH. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):e1-e48. doi: 10.1093/cid/cix1085.

  PMID: 29462280 BACKGROUND

MeSH Terms

Conditions

Enterocolitis, Pseudomembranous

Interventions

Fidaxomicin; Vancomycin

Condition Hierarchy (Ancestors)

Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Emily McDonald, MD MSc

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

  PRINCIPAL INVESTIGATOR

• Todd Lee, MSc MPH

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Connor Prosty, MD

CONTACT

514-934-1934; connor.prosty@mail.mcgill.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: November 25, 2025
• First Posted: January 9, 2026
• Study Start: April 24, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): November 1, 2030
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)