Oral vancomycin to prevent C. difficile infection in critically ill adults

Enteral Vancomycin as Primary Prophylaxis Against Clostridioides Difficile Infection in Critically Ill Patients

Phase2; Phase3 Interventional Riverside University Health System Medical Center · NCT07221370

This trial sees if taking oral vancomycin can prevent C. difficile infection in critically ill adults who are receiving systemic antibiotics.

Quick facts

PhasePhase2; Phase3
Study typeInterventional
Enrollment176 (estimated)
Ages18 Years and up
SexAll
SponsorRiverside University Health System Medical Center Academic / other
Drugs / interventionschemotherapy, prednisone
Locations1 site (Moreno Valley, California)
Trial IDNCT07221370 on ClinicalTrials.gov

What this trial studies

This randomized, placebo-controlled trial enrolls critically ill adults hospitalized at least 72 hours who have received systemic antibiotics for at least 72 hours and meet additional high-risk criteria for C. difficile. Participants are randomized to receive enteral vancomycin 125 mg daily or a matching placebo while on systemic antibiotics and for up to five days after the last antibiotic dose. Investigators will monitor healthcare facility-onset C. difficile infection rates, C. difficile carriage and clearance using rectal swabs, and safety outcomes including vancomycin-resistant enterococci emergence. The study is designed to test whether short-course prophylactic enteral vancomycin can lower CDI incidence without causing unacceptable harms in this high-risk hospitalized population.

Who should consider this trial

Good fit: Adults (≥18 years) hospitalized ≥72 hours who have received ≥72 hours of systemic antibiotics and have at least two additional high-risk features (for example age ≥65, PPI use, immunocompromise, ESRD, recent hospitalization).

Not a fit: Patients with prior history of C. difficile infection, those expected to require prolonged antibiotics (>14 days), those on excluded concurrent therapies (such as chronic probiotics or metronidazole per protocol), pregnant or breastfeeding individuals, and currently incarcerated persons are unlikely to be eligible or to receive benefit from this protocol.

Why it matters

Potential benefit: If effective, prophylactic oral vancomycin could lower C. difficile infection rates and related complications in high-risk hospitalized adults.

How similar studies have performed: Observational and small single-center studies have suggested enteral vancomycin may reduce CDI in certain high-risk groups, but large randomized evidence for primary prophylaxis is limited.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

1. Must meet all 3 criteria:

   * Adults aged 18 years and older.
   * Receiving ≥ 72 hours of a systemic antibiotic during index hospitalization.
   * Admitted ≥ 72 hours into their index hospitalization.
2. And must meet 2 additional of the following high-risk criteria

   * Age ≥ 65 years
   * Previous residence in long-term care facility
   * Previous proton pump inhibitor use (chronic or as needed)
   * Inflammatory bowel disease
   * Immunocompromised state (HIV/AIDS; transplant recipient; receipt of prednisone 20 mg daily for at least one month, immunosuppressants, or chemotherapy)
   * End stage renal disease (ESRD)
   * Diabetes mellitus
   * Receipt of catecholamines (norepinephrine at a rate of ≥ 5 mcg/min)
   * Hospitalized ≤ 30 days prior to the index hospitalization.
   * Received systemic antibiotics during that prior hospitalization.

Exclusion Criteria:

* Pregnant or breastfeeding women
* Currently incarcerated individuals
* Individual or legal representative whose informed consent cannot be obtained
* Subject not expected to survive the ICU stay or subject likely to be considered for palliative or hospice care
* Receiving concurrent treatment with metronidazole for any indication
* One-time empiric use of metronidazole is allowed and does not constitute an exclusion criterion
* Receiving concurrent probiotics
* Allergic reaction or had a contraindication for use of enteral vancomycin
* History of prior CDI within the past 90 days of randomization
* Had suspected active CDI prior to inclusion
* Infection requiring more than 14 21 days of systemic antibiotics during index hospitalization

Where this trial is running

Moreno Valley, California

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Clostridium Difficile InfectionVancomycin Resistant Enterococci InfectionClostridium difficle infectionprimary prophylaxisVancomycin resistant enterocci infection
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.