Clostridium Difficile Infection
Conditions
Brief summary
The goal of this study is to evaluate whether using vancomycin orally can prevent CDI in patients who are colonized with C. difficile who are admitted to the hospital and need antibiotics for another infection.
Detailed description
Screening to Prophylax against CDI (SToP CDI) is a prospective, single-center, double-blinded, randomized, placebo-controlled study of the effectiveness of vancomycin vs. placebo for preventing CDI in patients colonized with toxigenic C. difficile and receiving high-risk antibiotics. The investigators plan to screen 2500 patients to randomize 200. Consented patients will have a stool sample collected and tested for presence of toxigenic C. difficile by polymerase chain reaction (PCR) test. Patients who test negative will simply be followed for development, severity and outcome of CDI. Patients who test positive (are colonized with C. difficile) will be randomized to one of two arms: Arm 1: Patients receive 125 mg vancomycin by mouth (PO) every 6 hours as prophylaxis against C. difficile for the duration of their antibiotic treatment +3 days. Arm 2: Patients receive placebo by mouth (PO) every 6 hours for the duration of their antibiotic treatment +3 days.
Interventions
DRUGVancomycin
OTHERPlacebo
Sponsors
Corewell Health East
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Expected duration of admission sufficient to complete screening and enrollment 2. Age ≥18 3. Able to give informed consent 4. Initiated on one of the following antibiotics within the prior 72 hours with an expected duration of at least 72 hours from enrollment: clindamycin, ampicillin, ampicillin/sulbactam, amoxicillin, amoxicillin/clavulanate, moxifloxacin, levofloxacin, piperacillin/tazobactam, or any cephalosporin 5. Maximum expected duration of antibiotics 8 weeks 6. Able to take oral study medications 7. Able to provide a stool sample during hospitalization or within 3 days of discharge 8. Reasonably expected to be able to complete follow up
Exclusion criteria
1. Chron's disease, ulcerative colitis, celiac disease, or other chronic diarrheal illness 2. CDI within prior 90 days 3. Currently on metronidazole, oral vancomycin, rifaximin, fidaxomicin, or any other antibiotic active against C. difficile 4. Current diarrhea 5. Current ileostomy, colostomy or other form of surgically disconnected gut such that oral therapy would not be expected to reach the entire lumen of the gut 6. Pregnancy or breast feeding (determined prior to randomization) 7. Travel to an area of endemic diarrheal illness within the last 30 days 8. Life expectancy of less than 60 days 9. Known allergy to vancomycin 10. Participation with other research trials that could impact the results of this trial within the last 30 days 11. Previously enrolled in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence of CDI in Inpatients Receiving Vancomycin Prophylaxis vs. Placebo Who Are on High-risk Antibiotics and Are Colonized With Toxigenic C. Difficile. | 12 weeks after treatment | Number of participants with CDI in this subgroup of patients as assessed by clinical presentation, polymerase chain reaction (PCR) testing of stool, and EIA test for production of toxins. Patients are considered to have CDI if they have a positive PCR test, a positive toxin enzyme immunoassay (EIA) test, and clinical symptoms compatible with CDI. This outcome is only applicable to the two randomized arms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Severity of CDI in Patients Receiving Vancomycin Prophylaxis vs. Placebo. | 12 weeks after treatment | Number of randomized participants with mild, moderate, severe or fulminant disease after treatment. This outcome is only applicable to the two randomized arms. |
| The Outcome of CDI in Patients Receiving Vancomycin Prophylaxis vs. Placebo. | 12 weeks after treatment | Number of participants who developed C difficile infection after treatment. This outcome is only applicable to the two randomized arms. |
| The Prevalence of Toxigenic C. Difficile Colonization Among the Inpatient Population Treated With High-risk Antibiotics Based on C. Difficile PCR. | 12 weeks after treatment | Number of participants who remained colonized with C. difficile after treatment. This outcome is only applicable to the two randomized arms. |
| The Incidence of CDI in Patients Initiated on High Risk Antibiotics Who Are Not Colonized With Toxigenic C. Difficile. | 12 weeks after antibiotics | Number of participants who developed CDI in this subgroup of patients as assessed by clinical presentation and PCR testing of stool. Patients are considered to have CDI if they have a positive PCR test and clinical symptoms compatible with CDI. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited based on initiation of high-risk antibiotic treatment for a minimum expedited duration of three days, between December 15, 2016 and June 30, 2023. The first participant was enrolled on December 19, 2016 and the last participant was enrolled June 28, 2023.
Pre-assignment details
Of 1294 participants consented, 728 provided stool samples. 81 met inclusion criteria of culture of stool sample verifying presence of toxigenic C. difficile, and of these 81, 27 consented to randomization to treatment with vancomycin or placebo. These 27 participants are listed in the randomized participant flow below (placebo group or vancomycin group). 647 participants who screened negative and who were not randomized were available for analysis for secondary outcome 5.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients who screened positive for the presence of C. difficile colonization were randomized to one of two groups: The Placebo group received a placebo liquid every 6 hours. A placebo will look like the drug being studied, but have no active ingredients, in this case it will be fruit punch with vitamins added to mimic the taste of vancomycin.
Placebo | 14 |
| Vancomycin Patients who screened positive for the presence of C. difficile colonization were randomized to one of two groups: the Study group received Vancomycin 125 mg by mouth every 6 hours
Vancomycin | 13 |
| Screened Negative for C. Difficile Colonization Patients who screened negative at enrollment for the presence of C. difficile were not eligible for the randomized portion of the trial, but were available analysis of secondary outcome 5. | 647 |
| Total | 674 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Vancomycin | Screened Negative for C. Difficile Colonization |
|---|---|---|---|---|
| Age, Continuous | 63.8 years STANDARD_DEVIATION 15.3 | 68.44 years STANDARD_DEVIATION 17.57 | 68.6 years STANDARD_DEVIATION 15.5 | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | — |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 25 Participants | 13 Participants | — |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants | — |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 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 | 1 Participants | 0 Participants | — |
| Race (NIH/OMB) White | 13 Participants | 25 Participants | 12 Participants | — |
| Region of Enrollment United States | 14 participants | 27 participants | 13 participants | 647 participants |
| Sex: Female, Male Female | 8 Participants | 14 Participants | 6 Participants | — |
| Sex: Female, Male Male | 6 Participants | 13 Participants | 7 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 1 / 13 |
| other Total, other adverse events | 8 / 14 | 8 / 13 |
| serious Total, serious adverse events | 4 / 14 | 4 / 13 |
Outcome results
Primary
The Incidence of CDI in Inpatients Receiving Vancomycin Prophylaxis vs. Placebo Who Are on High-risk Antibiotics and Are Colonized With Toxigenic C. Difficile.
Number of participants with CDI in this subgroup of patients as assessed by clinical presentation, polymerase chain reaction (PCR) testing of stool, and EIA test for production of toxins. Patients are considered to have CDI if they have a positive PCR test, a positive toxin enzyme immunoassay (EIA) test, and clinical symptoms compatible with CDI. This outcome is only applicable to the two randomized arms.
Time frame: 12 weeks after treatment
Population: Data not available for 3 patients lost to follow-up/withdrawn in placebo arm and 4 patients lost to follow-up/withdrawn and 1 death in vancomycin arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | The Incidence of CDI in Inpatients Receiving Vancomycin Prophylaxis vs. Placebo Who Are on High-risk Antibiotics and Are Colonized With Toxigenic C. Difficile. | 0 Participants |
| Vancomycin | The Incidence of CDI in Inpatients Receiving Vancomycin Prophylaxis vs. Placebo Who Are on High-risk Antibiotics and Are Colonized With Toxigenic C. Difficile. | 0 Participants |
Secondary
The Incidence of CDI in Patients Initiated on High Risk Antibiotics Who Are Not Colonized With Toxigenic C. Difficile.
Number of participants who developed CDI in this subgroup of patients as assessed by clinical presentation and PCR testing of stool. Patients are considered to have CDI if they have a positive PCR test and clinical symptoms compatible with CDI.
Time frame: 12 weeks after antibiotics
Population: Patients were originally screened for C. difficile colonization prior to randomization. This population represents the 647 participants who initially screened negative for C. difficile colonization and were not placed into the randomized portion of the study, but were assessed at 12 weeks for C. difficile infection. This outcome is not applicable to the colonized, randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | The Incidence of CDI in Patients Initiated on High Risk Antibiotics Who Are Not Colonized With Toxigenic C. Difficile. | 4 Participants |
Secondary
The Outcome of CDI in Patients Receiving Vancomycin Prophylaxis vs. Placebo.
Number of participants who developed C difficile infection after treatment. This outcome is only applicable to the two randomized arms.
Time frame: 12 weeks after treatment
Population: Data not available for 3 patients lost to follow-up/withdrawn in placebo arm and 4 patients lost to follow-up/withdrawn and 1 death in vancomycin arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | The Outcome of CDI in Patients Receiving Vancomycin Prophylaxis vs. Placebo. | 0 Participants |
| Vancomycin | The Outcome of CDI in Patients Receiving Vancomycin Prophylaxis vs. Placebo. | 0 Participants |
Secondary
The Prevalence of Toxigenic C. Difficile Colonization Among the Inpatient Population Treated With High-risk Antibiotics Based on C. Difficile PCR.
Number of participants who remained colonized with C. difficile after treatment. This outcome is only applicable to the two randomized arms.
Time frame: 12 weeks after treatment
Population: Data not available for 3 patients withdrawn/lost to follow-up in the placebo arm, and 4 patients withdrawn/lost to follow-up plus one death in the vancomycin arm. One patient in the placebo arm did not give a stool sample.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | The Prevalence of Toxigenic C. Difficile Colonization Among the Inpatient Population Treated With High-risk Antibiotics Based on C. Difficile PCR. | 5 Participants |
| Vancomycin | The Prevalence of Toxigenic C. Difficile Colonization Among the Inpatient Population Treated With High-risk Antibiotics Based on C. Difficile PCR. | 5 Participants |
Secondary
The Severity of CDI in Patients Receiving Vancomycin Prophylaxis vs. Placebo.
Number of randomized participants with mild, moderate, severe or fulminant disease after treatment. This outcome is only applicable to the two randomized arms.
Time frame: 12 weeks after treatment
Population: Data not available for 3 patients withdrawn/lost to follow-up in placebo arm and 4 patients withdrawn/lost to follow-up and 1 death in vancomycin arm.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | The Severity of CDI in Patients Receiving Vancomycin Prophylaxis vs. Placebo. | moderate | 0 Participants |
| Placebo | The Severity of CDI in Patients Receiving Vancomycin Prophylaxis vs. Placebo. | fulminant | 0 Participants |
| Placebo | The Severity of CDI in Patients Receiving Vancomycin Prophylaxis vs. Placebo. | severe | 0 Participants |
| Placebo | The Severity of CDI in Patients Receiving Vancomycin Prophylaxis vs. Placebo. | no disease | 11 Participants |
| Placebo | The Severity of CDI in Patients Receiving Vancomycin Prophylaxis vs. Placebo. | mild | 0 Participants |
| Vancomycin | The Severity of CDI in Patients Receiving Vancomycin Prophylaxis vs. Placebo. | no disease | 8 Participants |
| Vancomycin | The Severity of CDI in Patients Receiving Vancomycin Prophylaxis vs. Placebo. | mild | 0 Participants |
| Vancomycin | The Severity of CDI in Patients Receiving Vancomycin Prophylaxis vs. Placebo. | moderate | 0 Participants |
| Vancomycin | The Severity of CDI in Patients Receiving Vancomycin Prophylaxis vs. Placebo. | severe | 0 Participants |
| Vancomycin | The Severity of CDI in Patients Receiving Vancomycin Prophylaxis vs. Placebo. | fulminant | 0 Participants |