CDI, C. Diff Colitis, C.Difficile Colitis, C.Difficile Diarrhea, Clostridium Difficile Infection, Recurrent Clostridium Difficile Infection
Conditions
Keywords
Oral vancomycin, vancomycin, antibiotic
Brief summary
This study evaluates the efficacy of prophylaxis with oral vancomycin for preventing recurrent Clostridium difficile Infection (CDI) in patients who have experienced at least one CDI episode in the last 180 days and are receiving antibiotics for a non CDI condition. Participants will be randomized to receive either placebo or oral vancomycin in addition to their prescribed antibiotic therapy.
Detailed description
Many patients who have a CDI experience recurrent or relapsing symptoms. The investigators are studying whether vancomycin in low doses will help prevent further CDI episodes and how this therapy impacts patients' gastrointestinal microbiome and composition. Patients with a history of past CDI who are receiving antibiotics for a non-CDI condition will be invited to participate. Approximately half of the participants will receive a low-dose capsule of vancomycin and half will receive a placebo. Participants will continue taking the vancomycin/placebo for 5 days after their prescribed antibiotics end.
Interventions
DRUGVancomycin
Vancomycin capsule, 125 mg
DRUGPlacebo
Capsule containing inert (nonactive) material to mimic 125 mg vancomycin capsule
Sponsors
Medical College of Wisconsin
Agency for Healthcare Research and Quality (AHRQ)
Henry Ford Hospital
Mayo Clinic
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing to provide informed consent. * Willing to comply with all study procedures and be available for the duration of the study. * Documented diagnosis of at least one CDI within the last 180 days with treatment completed. * Currently receiving systemic antibiotics for a non-CDI condition with anticipated duration of no more than 2 weeks. * Females of childbearing potential must have a negative pregnancy test prior to randomization and agree to use adequate contraception prior to randomization, for the duration of the study, and for 4 weeks following study completion. * Have received no more than 72 hours of non-CDI antibiotics.
Exclusion criteria
* History of hypersensitivity or allergy to oral vancomycin. * Current use of oral vancomycin * Patients on concurrent treatment with metronidazole or tetracycline monotherapy for any indication * Patients diagnosed with inflammatory bowel disorder (Crohn's disease), or bacterial gastrointestinal infection cause by agents other than C. difficile (e.g. Salmonella sp.), toxic megacolon and/or known small bowel ileus. * Dysphagia (inability to swallow capsules) or unwilling to swallow capsules. * Major gastrointestinal surgery within 3 months of enrollment (does not include appendectomy or cholecystectomy). * Any history of total colectomy or bariatric surgery. * Unable or unwilling to fulfill study requirements. * Expected life expectancy \< 6 months. * Patients enrolled in another clinical trial with investigational drugs within 30 days prior to randomization. * Women who are pregnant or breast-feeding. * Any patient deemed not suitable for study participation at the discretion of the study investigator. * Diarrhea (3 or more loose stools in a 24 hour period) at enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrent Clostridium Difficile Infection (CDI) | 8 weeks | Determine whether CDI recurrence is decreased in patients taking oral vancomycin as prophylactic therapy in addition to standard-of-care antibiotics that patients are taking for non-CDI reasons. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gut Microbiome Composition | 8 weeks | Study how the gut microbiome is altered in patients receiving vancomycin treatment compared to placebo. |
| Vancomycin-resistant Enterococcus (VRE) Colonization in Stool Samples of Patients Receiving Vancomycin vs. Patients Receiving Placebo | 8 weeks | Low-dose exposure to vancomycin and VRE infection has not been studied. We will examine the incidence of VRE colonization in stool samples of all patients and determine whether oral vancomycin increases the VRE colonization rate, which has a negative impact on the overall health of patients being treated with vancomycin for C. difficile infection. |
| Determine Whether Clostridium Difficile Positivity on Any Stool Sample is a Predictor of CDI Recurrence. | 8 weeks | Stool samples will be tested at baseline, at the last dose date of vancomycin or placebo, at approximately 8 weeks following the last dose of vancomycin or placebo, and as indicated for diarrhea symptoms. Samples will be collected and tested for the presence of Clostridium difficile. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vancomycin 125 mg, oral capsule by mouth, once daily, for the duration of standard-of-care antibiotic therapy plus 5 days
Vancomycin: Vancomycin capsule, 125 mg | 37 |
| Placebo 125 mg placebo capsule by mouth, once daily, for the duration of standard-of-care antibiotic therapy plus 5 days
Placebo: Capsule containing inert (nonactive) material to mimic 125 mg vancomycin capsule | 42 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Lack of Efficacy | 2 | 4 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Unable to complete doses of study drug/placebo | 0 | 3 |
| Overall Study | Unable to obtain stool samples at visit | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Vancomycin | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 58.89 years STANDARD_DEVIATION 15 | 58.65 years STANDARD_DEVIATION 14 | 58.40 years STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 76 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 9 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 33 Participants | 67 Participants | 34 Participants |
| Region of Enrollment United States | 37 Participants | 79 Participants | 42 Participants |
| Sex: Female, Male Female | 24 Participants | 49 Participants | 25 Participants |
| Sex: Female, Male Male | 13 Participants | 30 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 37 | 2 / 42 |
| other Total, other adverse events | 37 / 37 | 42 / 42 |
| serious Total, serious adverse events | 9 / 37 | 10 / 42 |
Outcome results
Primary
Recurrent Clostridium Difficile Infection (CDI)
Determine whether CDI recurrence is decreased in patients taking oral vancomycin as prophylactic therapy in addition to standard-of-care antibiotics that patients are taking for non-CDI reasons.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vancomycin | Recurrent Clostridium Difficile Infection (CDI) | 17 Participants |
| Placebo | Recurrent Clostridium Difficile Infection (CDI) | 24 Participants |
p-value: 0.2295% CI: [-35.1, 8]Chi-squared
Secondary
Determine Whether Clostridium Difficile Positivity on Any Stool Sample is a Predictor of CDI Recurrence.
Stool samples will be tested at baseline, at the last dose date of vancomycin or placebo, at approximately 8 weeks following the last dose of vancomycin or placebo, and as indicated for diarrhea symptoms. Samples will be collected and tested for the presence of Clostridium difficile.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Vancomycin | Determine Whether Clostridium Difficile Positivity on Any Stool Sample is a Predictor of CDI Recurrence. | NA stool samples |
| Placebo | Determine Whether Clostridium Difficile Positivity on Any Stool Sample is a Predictor of CDI Recurrence. | NA stool samples |
Secondary
Gut Microbiome Composition
Study how the gut microbiome is altered in patients receiving vancomycin treatment compared to placebo.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Vancomycin | Gut Microbiome Composition | NA stool samples |
| Placebo | Gut Microbiome Composition | NA stool samples |
Secondary
Vancomycin-resistant Enterococcus (VRE) Colonization in Stool Samples of Patients Receiving Vancomycin vs. Patients Receiving Placebo
Low-dose exposure to vancomycin and VRE infection has not been studied. We will examine the incidence of VRE colonization in stool samples of all patients and determine whether oral vancomycin increases the VRE colonization rate, which has a negative impact on the overall health of patients being treated with vancomycin for C. difficile infection.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vancomycin | Vancomycin-resistant Enterococcus (VRE) Colonization in Stool Samples of Patients Receiving Vancomycin vs. Patients Receiving Placebo | 15 Participants |
| Placebo | Vancomycin-resistant Enterococcus (VRE) Colonization in Stool Samples of Patients Receiving Vancomycin vs. Patients Receiving Placebo | 6 Participants |
p-value: 0.1Proportional difference test