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

Hamilton Health Sciences (HHS)

Status and phase: Withdrawn; Early Phase 1

Conditions: Clostridium Difficile Colonization; Clostridium Difficile Diarrhea

Treatments: Dietary Supplement: Culturelle; Drug: Probiotic Placebo; Drug: Vancomycin Placebo; Drug: Vancomycin

Study type: Interventional

Funder types: Other

Identifiers

NCT04246151

DECENCY-RCT

Details and patient eligibility

About

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.

Full description

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

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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0 participants in 3 patient groups, including a placebo group

Vancomycin & probiotic placebo

Experimental group

Description:

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.

Treatment:

Drug: Vancomycin

Drug: Probiotic Placebo

Probiotic & vancomycin placebo

Experimental group

Description:

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.

Treatment:

Drug: Vancomycin Placebo

Dietary Supplement: Culturelle

Probiotic placebo & vancomycin placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Probiotic Placebo

Drug: Vancomycin Placebo