Efficacy of Oral Vancomycin Prophylaxis for Prevention of Recurrent Clostridium Difficile Infection

Phase 2

Completed

• Conditions: CDI; C.Difficile Colitis; C. Diff Colitis; C.Difficile Diarrhea; Recurrent Clostridium Difficile Infection; Clostridium Difficile Infection
• Interventions: Drug: Placebo; Drug: Vancomycin

• Registration Number: NCT03462459
• Lead Sponsor: University of Wisconsin, Madison

Brief Summary

This study evaluates the efficacy of prophylaxis with oral vancomycin for preventing recurrent Clostridium difficile Infection (CDI) in patients who have experienced at least one CDI episode in the last 180 days and are receiving antibiotics for a non CDI condition. Participants will be randomized to receive either placebo or oral vancomycin in addition to their prescribed antibiotic therapy.

Detailed Description

Many patients who have a CDI experience recurrent or relapsing symptoms. The investigators are studying whether vancomycin in low doses will help prevent further CDI episodes and how this therapy impacts patients' gastrointestinal microbiome and composition.

Patients with a history of past CDI who are receiving antibiotics for a non-CDI condition will be invited to participate. Approximately half of the participants will receive a low-dose capsule of vancomycin and half will receive a placebo. Participants will continue taking the vancomycin/placebo for 5 days after their prescribed antibiotics end.

Study Timeline

• Study First Submitted: 2018-02-28
• Study First Submitted QC: 2018-03-08
• Study First Posted: 2018-03-12
• Study Start: 2018-05-21
• Primary Completion: 2023-07-06
• Study Completion: 2023-07-06
• Results First Submitted: 2024-11-01
• Status Verified: 2025-05
• Results First Submitted QC: 2025-05-07
• Last Update Submitted: 2025-05-07
• Results First Posted: 2025-05-25
• Last Update Posted: 2025-05-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 79

Inclusion Criteria

• Willing to provide informed consent.
• Willing to comply with all study procedures and be available for the duration of the study.
• Documented diagnosis of at least one CDI within the last 180 days with treatment completed.
• Currently receiving systemic antibiotics for a non-CDI condition with anticipated duration of no more than 2 weeks.
• Females of childbearing potential must have a negative pregnancy test prior to randomization and agree to use adequate contraception prior to randomization, for the duration of the study, and for 4 weeks following study completion.
• Have received no more than 72 hours of non-CDI antibiotics.

Exclusion Criteria

• History of hypersensitivity or allergy to oral vancomycin.
• Current use of oral vancomycin
• Patients on concurrent treatment with metronidazole or tetracycline monotherapy for any indication
• Patients diagnosed with inflammatory bowel disorder (Crohn's disease), or bacterial gastrointestinal infection cause by agents other than C. difficile (e.g. Salmonella sp.), toxic megacolon and/or known small bowel ileus.
• Dysphagia (inability to swallow capsules) or unwilling to swallow capsules.
• Major gastrointestinal surgery within 3 months of enrollment (does not include appendectomy or cholecystectomy).
• Any history of total colectomy or bariatric surgery.
• Unable or unwilling to fulfill study requirements.
• Expected life expectancy < 6 months.
• Patients enrolled in another clinical trial with investigational drugs within 30 days prior to randomization.
• Women who are pregnant or breast-feeding.
• Any patient deemed not suitable for study participation at the discretion of the study investigator.
• Diarrhea (3 or more loose stools in a 24 hour period) at enrollment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	125 mg placebo capsule by mouth, once daily, for the duration of standard-of-care antibiotic therapy plus 5 days
Vancomycin	Vancomycin	125 mg, oral capsule by mouth, once daily, for the duration of standard-of-care antibiotic therapy plus 5 days

Primary Outcome Measures

Name	Time	Method
Recurrent Clostridium Difficile Infection (CDI)	8 weeks	Determine whether CDI recurrence is decreased in patients taking oral vancomycin as prophylactic therapy in addition to standard-of-care antibiotics that patients are taking for non-CDI reasons.

Secondary Outcome Measures

Name	Time	Method
Gut Microbiome Composition	8 weeks	Study how the gut microbiome is altered in patients receiving vancomycin treatment compared to placebo.
Vancomycin-resistant Enterococcus (VRE) Colonization in Stool Samples of Patients Receiving Vancomycin vs. Patients Receiving Placebo	8 weeks	Low-dose exposure to vancomycin and VRE infection has not been studied. We will examine the incidence of VRE colonization in stool samples of all patients and determine whether oral vancomycin increases the VRE colonization rate, which has a negative impact on the overall health of patients being treated with vancomycin for C. difficile infection.
Determine Whether Clostridium Difficile Positivity on Any Stool Sample is a Predictor of CDI Recurrence.	8 weeks	Stool samples will be tested at baseline, at the last dose date of vancomycin or placebo, at approximately 8 weeks following the last dose of vancomycin or placebo, and as indicated for diarrhea symptoms. Samples will be collected and tested for the presence of Clostridium difficile.

Trial Locations

Locations (2)

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

University of Wisconsin-Madison; 🇺🇸 Madison, Wisconsin, United States