Oral Vancomycin Versus Probiotics Versus Placebo for Prevention of Clostridium Difficile Infection in Colonized Patients

NCT04246151 | Withdrawn Early Phase 1 DMC

• 1 other identifier: DECENCY-RCT
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Clostridium Difficile Colonization; Clostridium Difficile Diarrhea

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (3)

Vancomycin & probiotic placebo

EXPERIMENTAL

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; Drug: Probiotic Placebo

Probiotic & vancomycin placebo

EXPERIMENTAL

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; Drug: Vancomycin Placebo

Probiotic placebo & vancomycin placebo

PLACEBO COMPARATOR

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: Vancomycin Placebo; Drug: Probiotic Placebo

Interventions

Vancomycin DRUG

Vancomycin capsules

Also known as: JAMP-vancomycin

Vancomycin & probiotic placebo

Culturelle DIETARY_SUPPLEMENT

Culturelle capsules

Also known as: Lactobacillus rhamnosus GG

Probiotic & vancomycin placebo

Vancomycin Placebo DRUG

sugar pill manufactured to mimic the vancomycin 125 mg capsule

Also known as: Placebo for Vancomycin

Probiotic & vancomycin placebo; Probiotic placebo & vancomycin placebo

Probiotic Placebo DRUG

sugar pill manufactured to mimic 10 billion unit probiotic capsules.

Also known as: Placebo for probiotic

Probiotic placebo & vancomycin placebo; Vancomycin & probiotic placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hamilton Health Sciences Corporation: lead

Study Sites (2)

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 4A6, Canada

Location

Hamilton Health Sciences

Hamilton, Ontario, L8V 1C3, Canada

Location

MeSH Terms

Interventions

Vancomycin; Probiotics

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Blinding will be done in a double-blind fashion. The patients, their caregiver, and the investigator will be blinded to the study treatment.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomized to receive either a probiotic, oral vancomycin, or placebo in a parallel-group 1:1:1 design.

Study Record Dates

• First Submitted: January 20, 2020
• First Posted: January 29, 2020
• Study Start: September 1, 2022
• Primary Completion: September 12, 2024
• Study Completion: September 12, 2024
• Last Updated: February 20, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)