Clostridioides Difficile Infection, Inflammatory Bowel Disease (IBD)
Conditions
Keywords
C. difficile, Crohn's Disease, Ulcerative Colitis
Brief summary
This is a randomized, double-blind study to assess the safety and efficacy of fidaxomicin compared to vancomycin for decolonization of C. difficile in IBD patients. A total of 60 patients who meet eligibility criteria will be randomized 1:1 to either the fidaxomicin or vancomycin arm. The vancomycin arm will receive a dose of 125 mg PO q 6 hours for 10 days. The fidaxomicin arm will receive 200 mg PO BID for 10 days. In order to ensure blinding, both antibiotics will be concealed in opaque 00 capsule shells. In addition, those in the fidaxomicin arm will receive 2 placebo capsules so that all participants will receive 4 capsules daily for 10 days. Microbiome assessment and C. difficile testing will be performed at baseline, day 5, day 10, and weeks 4, 8, and 26.
Detailed description
This randomized, double-blind trial will assess the ability of fidaxomicin compared to vancomycin to decolonize C. difficile in the IBD patient population. Participants who meet eligibility criteria will be randomized 1:1 to either vancomycin or fidaxomicin treatment. The vancomycin arm will receive a dose of 125 mg PO q 6 hours for 10 days. The fidaxomicin arm will receive 200 mg PO BID for 10 days. In order to ensure blinding both antibiotics will be concealed in opaque 00 capsule shells. In addition, those in the fidaxomicin arm will receive 2 placebo capsules so that all participants will receive 4 capsules daily for 10 days. Participants will end dosing after 10 days, but monitoring will continue to week 8. Both participants and study team will be blinded to treatment arm allocation. Participants will be assessed through week 8 for the primary outcome, decolonization. Safety and tolerability outcomes will be assessed through week 8. In addition, secondary efficacy outcomes including IBD disease activity and development of CDI will be evaluated at week 8 and week 26. Participants will also be followed through week 26 for long-term safety, efficacy, and clinical outcomes. Disease activity and symptoms will be recorded from time of informed consent through to the week 26 trial visit. Stool samples for biomarker assessments and C. difficile testing will be collected at scheduled trial visits per Schedule of Assessments. The primary outcome, decolonization of C. Difficile at week 8, will be confirmed via stool sampling. Additional C. difficile testing will be done at week 26. Participants that experience intolerable adverse events will be withdrawn from the study and will be considered treatment failures. Additional subjects may be enrolled to obtain 60 patients with week 8 data. The study will enroll approximately 60 adult participants at a single center.
Interventions
DRUGVancomycin (POC)
Vancomycin is glycopeptide antibiotic that has broad gram-positive coverage. Patients will receive 125mg PO every 6 hours for 10 days.
DRUGFidaxomicin
Fidaxomicin is a macrolide antibiotic. It is narrow spectrum with potent bactericidal activity specifically against C. difficile. Patients will receive 200mg PO twice daily for 10 days.
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent. 2. Male or female \> 18 years of age. 3. IBD diagnosis (CD, UC or indeterminant Colitis will be permitted.) 4. Presenting for outpatient colonoscopy for any indication.
Exclusion criteria
1. Unable to provide consent. 2. Patients with previous colectomy, ostomy, J-pouch, or previous colon surgery (excluding appendectomy.) 3. Unable to complete study procedures. 4. Chronic use of antibiotics. 5. Inability or unwillingness to swallow capsules. 6. Allergy or sensitivity to vancomycin, fidaxomicin, or microcrystalline cellulose.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| C. difficile decolonization | 8 weeks | Absence of C. difficile via PCR in Week 8 stool sample |
| Safety and tolerability | 8 weeks | Subject incidence of treatment-emergent adverse events (including treatment-emergent adverse events for clinically significant changes in laboratory parameters and vital signs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biomass of C. difficile | 8 weeks | Change in stool C. difficile biomass in patients at week 8 by quantitative culture and qPCR |
| Long-term effect of C. difficile decolonization on IBD clinical outcomes | 26 weeks | Change in IBD clinical scores from baseline at week 8 and week 26. IBD clinical scores are used to assess IBD patient symptoms. The assessments are separated between scores for Ulcerative Colitis (UC) and Crohn's Disease (CD). The Harvey Bradshaw Index (HBI) is a clinical assessment for IBD patients with Crohn's disease while Partial Mayo Score is a clinical assessment for Ulcerative Colitis. The scores will be collected at study visit in form of a survey. The HBI score can vary but a score above 8 or 9 is considered severe disease activity. The Partial Mayo Score can range from 0 to 9 and a score above 7 is considered severe disease activity. A decrease in score from baseline to follow-up timepoints is indicative of improved IBD patient symptoms. A decrease in score from baseline to follow-up timepoints is indicative of improved IBD patient symptoms. |
| C. difficile infection surveillance | 26 weeks | Incidence of patients developing CDI through Week 26 |
Countries
United States
Contacts
Primary ContactAlexander Carlin
Backup ContactJessica Allegretti, MD, MPH
Outcome results
None listed