Oral Vancomycin Versus Probiotics Versus Placebo for Prevention of Clostridium Difficile Infection in Colonized Patients (Decency-RCT)

Oral Vancomycin Versus Probiotics Versus Placebo for Prevention of Clostridium Difficile Infection in Colonized Patients (Decency-RCT): A Randomized Controlled Pilot Trial

The goal of this pilot study is to assess the feasibility of randomizing hospitalized patients that are colonized with C. difficile and started on systemic antibiotics to either a probiotic, oral vancomycin, or placebo in a parallel-group 1:1:1 design. The ultimate goal is to conduct an appropriately-powered RCT to determine the optimal method for reducing C difficile infection in colonized patients.

Study Overview

• Status: Recruiting
• Conditions: Clostridium Difficile Diarrhea; Clostridium Difficile Colonization
• Intervention / Treatment: Drug: Vancomycin; Drug: Probiotic Placebo; Dietary supplement: Culturelle; Drug: Vancomycin Placebo

Detailed Description

In this study, patients will be screened for C. difficile colonization

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Dominik Mertz, MD; Phone Number: 43952 905-525-9140; Email: Mertz@hhsc.ca
• Study Contact Backup: Name: Jodi Gilchrist, MSc; Phone Number: 33454 905-522-1155; Email: jgilchri@stjoes.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • Recruiting
      • St. Joseph's Healthcare Hamilton
      • Contact: Jodi Gilchrist, MSc; Phone Number: 33454 905-522-1155; Email: jgilchri@stjoes.ca
      • Contact: Marek Smieja, MD/PhD; Phone Number: 905-521-6021; Email: smiejam@mcmaster.ca
    • Hamilton, Ontario, Canada, L8V 1C3
      • Recruiting
      • Hamilton Health Sciences
      • Contact: Dominik Mertz, MD; Phone Number: 43952 905-525-9140; Email: Mertz@hhsc.ca
      • Contact: Jodi Gilchrist, MSc; Phone Number: 33454 905-522-1155; Email: jgilchri@stjoes.ca
      • Sub-Investigator: Mark Loeb, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult patients of 18 years of age or older identified as asymptomatic carriers of C. difficile (i.e. not meeting case definition of C. difficile infection, see below)
• Started on systemic (oral or intravenous) antibiotics for any (presumed) bacterial infection
• Patient must have vitals (heart rate, blood pressure, temperature), estimated creatinine clearance (using the Chronic Kidney Disease Epidemiology equation (CKD-Epi)) and a complete blood count available within 24 hours of enrolment

Exclusion Criteria:

• On a course of systemic antibiotics that had been started more than 72 hours ago (as current evidence suggests that the earlier probiotics are started, the more efficacious they are)
• Patient with C. difficile, i.e. presence of diarrhea (three or more loose or watery stools within 24 hours), or fevers or hypotension from C. difficile infection

• Any patients with contra-indications to probiotics or vancomycin:

  • Immunosuppressed (primary or acquired immunodeficiency, including AIDS (defined as AIDS defining condition or cluster of differentiation 4 (CD4) nadir of <200/ul), hematologic malignancies, long-term systemic corticosteroid treatment, active treatment with chemotherapeutic agents or biologicals, autoimmune diseases, nephrotic syndrome)
  • Structural heart disease (e.g. atrial septal defect, ventricular septal defect)
  • Gastroesophageal or compromised gut integrity (e.g. short gut syndrome, intestinal injury or dysfunction, inflammatory bowel diseases including current or past history of Crohn's disease and ulcerative colitis)
  • Patients on systemic aminoglycosides, ethacrynic acid, polymixin B, or colistin.
  • Prior or current hearing loss
  • Female patients with known pregnancy or who are planning to get pregnant, or who are breastfeeding
  • Patients with end-stage renal diseases defined as an estimated glomerular filtration rate of <15ml/min, or absence of a current estimated creatinine clearance
  • History of an allergic reaction to one of the study drugs, or sensitivity to milk
• Patients started on probiotics or oral vancomycin while in hospital

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vancomycin & probiotic placebo; Vancomycin 125 mg orally every 12 hours plus probiotic placebo orally every 12 hours for the duration of systematic antibiotic for a maximum of 21 days.	Drug: Vancomycin; Vancomycin capsules; Other Names: JAMP-vancomycin; Drug: Probiotic Placebo; sugar pill manufactured to mimic 10 billion unit probiotic capsules.; Other Names: Placebo for probiotic
Experimental: Probiotic & vancomycin placebo; Culturelle probiotic 20 billion active units orally every 12 hours plus vancomycin placebo orally every 12 hours for the duration of systematic antibiotic for a maximum of 21 days.	Dietary supplement: Culturelle; Culturelle capsules; Other Names: Lactobacillus rhamnosus GG; Drug: Vancomycin Placebo; sugar pill manufactured to mimic the vancomycin 125 mg capsule; Other Names: Placebo for Vancomycin
Placebo Comparator: Probiotic placebo & vancomycin placebo; Vancomycin placebo orally every 12 hours and Culturelle placebo orally every 12 hours for the duration of systematic antibiotic for a maximum of 21 days.	Drug: Probiotic Placebo; sugar pill manufactured to mimic 10 billion unit probiotic capsules.; Other Names: Placebo for probiotic; Drug: Vancomycin Placebo; sugar pill manufactured to mimic the vancomycin 125 mg capsule; Other Names: Placebo for Vancomycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients identified and randomized to a treatment arm within 72 hour of beginning a systematic antibiotic.	Feasibility will be assessed using the following parameters: Proportion of eligible participants screened that are randomized within 72 hours of antibiotic exposure (goal ≥ 90%); Proportion of participants receiving all doses of study medication (goal ≥ 90%); Proportion of participants with complete follow up at 14 days (goal ≥ 95%)	1 year
Development of C difficile associated diarrhea within 14 days of randomization	Development of C difficile associated diarrhea within 14 days of randomization to one of the treatment arms as defined by the Provincial Infectious Diseases Advisory Committee (PIDAC)	1 year

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): March 1, 2024

Study Registration Dates

• First Submitted: January 20, 2020
• First Submitted That Met QC Criteria: January 28, 2020
• First Posted (Actual): January 29, 2020

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Signs and Symptoms, Digestive; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Diarrhea; Clostridium Infections; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: DECENCY-RCT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No individual participant data will be shared with researchers that are not directly involved in this study. Overall data will be shared in the context of peer reviewed journal publications or scientific presentations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No