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

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.

Study Overview

• Status: Completed
• Conditions: Clostridium Difficile Infection; Recurrent Clostridium Difficile Infection; CDI; C.Difficile Diarrhea; C. Diff Colitis; C.Difficile Colitis
• Intervention / Treatment: Drug: Vancomycin; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin-Madison
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vancomycin; 125 mg, oral capsule by mouth, once daily, for the duration of standard-of-care antibiotic therapy plus 5 days	Drug: Vancomycin; Vancomycin capsule, 125 mg; Other Names: Vancocin; Vancomycin Hydrochloride
Placebo Comparator: Placebo; 125 mg placebo capsule by mouth, once daily, for the duration of standard-of-care antibiotic therapy plus 5 days	Drug: Placebo; Capsule containing inert (nonactive) material to mimic 125 mg vancomycin capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent Clostridium difficile infection (CDI)	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.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiome composition	Study how the gut microbiome is altered in patients receiving vancomycin treatment compared to placebo.	8 weeks
Vancomycin-resistant enterococcus (VRE) colonization in patients receiving vancomycin vs. placebo	Low-dose exposure to vancomycin and VRE infection has not been studied. We will examine the incidence of VRE colonization in all patients and determine whether oral vancomycin increases the VRE colonization rate.	8 weeks
Determine whether Clostridium difficile positivity on any stool sample is a predictor of CDI recurrence.	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.	8 weeks

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Mayo Clinic; Medical College of Wisconsin; Agency for Healthcare Research and Quality (AHRQ); Henry Ford Hospital
• Investigators: Principal Investigator: Nasia Safdar, MD PhD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2018
• Primary Completion (Actual): July 6, 2023
• Study Completion (Actual): July 6, 2023

Study Registration Dates

• First Submitted: February 28, 2018
• First Submitted That Met QC Criteria: March 8, 2018
• First Posted (Actual): March 12, 2018

Study Record Updates

• Last Update Posted (Actual): July 28, 2023
• Last Update Submitted That Met QC Criteria: July 26, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: antibiotic; vancomycin; Oral vancomycin
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease Attributes; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Recurrence; Diarrhea; Colitis; Clostridium Infections; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: 2017-0927; A534265 (Other Identifier: UW, Madison); 1R01HS025713-01 (U.S. AHRQ Grant/Contract); SMPH/MEDICINE/INFECT DIS (Other Identifier: UW Madison); Protocol ver 6, 18 Nov 2020 (Other Identifier: UW Madison)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No