Enteral Vancomycin as Primary Prophylaxis Against Clostridioides Difficile Infection in Critically Ill Patients
- Conditions
- Clostridium Difficile InfectionVancomycin Resistant Enterococci Infection
- Interventions
- Drug: Placebo
- Registration Number
- NCT07221370
- Brief Summary
The goal of this clinical trial is to determine if oral vancomycin can prevent C.diff infection in adults who are critically ill and are at high risk of C.diff infection due to their medical conditions and being in the hospital. It will also help us learn about the safety of the drug in this setting. The main questions the trial aims to answer are:
* Does oral vancomycin lower the rate of C.diff infection in high-risk patients?
* Does C.diff carrier status change the C.diff infection rate as well as clearance of carrier status when vancomycin is used as primary prophylaxis? Researchers will compare the oral, active drug vancomycin to a placebo (a look-alike substance that contains no drug) to determine if vancomycin works to prevent C.diff infection in the hospital.
Participants will:
* Take oral vancomycin or a placebo while they receive systemic antibiotic(s) for up to five days after the last dose of said systemic antibiotic(s). The treatment of said systemic antibiotic(s) is not to exceed 21 days.
* When discharged from the hospital, participants will continue to take the study medication in the event he/she did not complete the intended course of the study medication while in the hospital.
* Participants will provide stool sample or rectal swabs for to assess their C.diff carrier status as well as any change in stool microbiome status, including VRE (vancomycin resistant Enterococcus)
* After completion of the intervention period, participants will be contacted via telephone to assess if they developed diarrhea or any untoward effects of study medication.
- Detailed Description
Protocol Synopsis
General: Enteral vancomycin has gained attention as a promising strategy for preventing healthcare facility-onset Clostridioides difficile infection (HCFO-CDI) in patients during systemic antibiotic exposure in certain high-risk populations. However, data remain scarce for its use as primary prophylaxis. Our study aims to fill this gap and evaluate whether enteral vancomycin prophylaxis can reduce the incidence of HCFO-CDI in critically ill patients along with other relevant clinical outcomes.
Study Population: Study subjects will include hospitalized subjects with significant risk factors for HCFO-CDI. Inclusion and exclusion criteria are as follows:
Inclusion criteria: Adult patients with at least 72 hours of hospitalization who are on a systemic antibiotic for at least 72 hours presenting with two additional risk factors for the development of HCFO-CDI.
Exclusion criteria: Subjects whose consent cannot be obtained, those with concurrent use of probiotics or metronidazole (except for empiric use), those with an expected course of antibiotic for more than 14 days, those with a prior history of CDI, etc.
Study Intervention: Study subjects will be randomized into two study arms - treatment versus placebo. Those in the treatment arm will receive vancomycin 125 mg solution daily for up to five days after the last dose of systemic antibiotic. Those in the placebo arm will receive a matching placebo solution. A rectal swab will be performed on all subjects prior to randomization and at study termination or discharge to assess C. difficile colonization and the possible development of vancomycin-resistant Enterococcus colonization.
Primary outcome: Incidence of HCFO-CDI, defined as symptoms of ≥ 3 loose stools or diarrhea (in the absence of laxatives or other non-CDI causes) in a 24-hour period in subjects with concurrent positive stool test for C. difficile (polymerase chain reaction \[PCR\] and stool toxin test) \> 72 hours into hospitalization.
Enrollment period and sample size: First dose of enteral vancomycin or matching placebo will be administered within 72 hours of the first dose of systemic antibiotic. Study investigators will monitor the subjects for adherence and possible adverse events every 3 days until hospital discharge. We are planning 1:1 randomization of the study subjects in each group (placebo versus prophylaxis group). Utilizing a 2-sided α of 0.05 and 80% power, an estimated sample size is 176 (88 subject per arm). Sample size was determined by estimating a 0% incidence of HCFO-CDI in the prophylaxis arm and a 10% incidence of HCFO-CDI in the placebo arm based on historical and institutional data. We also anticipate a 20% drop out or attrition rate after randomization.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 176
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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.
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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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Oral Vancomycin 125 mg (liquid) Vancomycin 125mg Oral Vancomycin 125 mg (liquid) daily Placebo oral (liquid) Placebo Oral Placebo (liquid) daily.
- Primary Outcome Measures
Name Time Method Incidence the rate of healthcare facility-onset Clostridioides dificile infection (CDFO-CFI). up to 4 months Incidence of HCFO-CDI, defined as symptoms of ≥ 3 loose stools or diarrhea (in the absence of laxatives or other non-CDI causes) in a 24-hour period in subjects with concurrent positive stool test for C. difficile (polymerase chain reaction \[PCR\] and stool toxin test) \> 72 hours into hospitalization.
- Secondary Outcome Measures
Name Time Method Hospital length of stay (day) up to 30 days Hospital length of stay (day)
Incidence of Vancomycin Resistance Enterococcus (VRE) colonization in stool sample. up to 30 days The rate of emergence of VRE will be tested as a part of safety outcome. All enrolled subject into the study will have stool/rectal swab tested for VRE at the time of enrollment and end of the study/early termination.
Time to Clostridioides difficile infection in symptomatic patients up to 30 days Time to Clostridioides difficile infection in symptomatic patients
Rate community onset healthcare facility-associated CDI. up to 90 days Community-onset healthcare facility-associated CDI (CO-HFCA-CDI) will be assessed via telephonic surveys with the subjects 30- and 90-day post-discharge. CO-HFCA-CDI is defined as follows: subject's verbal confirmation of unexplained and new-onset ≥3 unformed stools in a 24-hour period since being discharged, subject seeking medical care for loose stools, and subject being diagnosed with CDI by a medical provider.
Clostridioides difficile colonization at discharge (PCR and toxin) up to 30 days Clostridioides difficile colonization at discharge (PCR and toxin)
In-hospital Mortality up to 30 days In-hospital mortality
Trial Locations
- Locations (1)
Riverside University Health System
🇺🇸Moreno Valley, California, United States
Riverside University Health System🇺🇸Moreno Valley, California, United StatesSuman B Thapamagar, MBBSContact9514864000suman.thapamagar@ruhealth.orgBrian Phan, PharmDSub InvestigatorSuman Thapamagar, MBBSPrincipal Investigator