Clostridium Difficile Infection
Conditions
Keywords
recurrent, infection
Brief summary
This is a medical research study designed to look at the safety and efficacy of 30-day course of fidaxomicin for treatment of recurrent CDI (Clostridium difficile Infection). CDI is an infection that results when the normal flora (resident bacteria) of the colon is substantially altered by antibiotic treatment. The decrease in this normal flora allows for the growth of the C. difficile bacteria. Fidaxomicin is an antibiotic which is approved by Health Canada for treatment of CDI. Only patients with a primary case of CDI or 1st episode of recurrent CDI have been studied using a 10-day course of fidaxomicin.
Detailed description
Clostridium difficile (C. difficile) infection (CDI) is one of the most frequent causes of healthcare associated infections and its rates are also growing in the community. The efficacy of standard antibiotics especially for recurrent CDI is limited as oral vancomycin and metronidazole also suppress the growth of anaerobic bacteria such as Bacteroides fragilis group which protect against proliferation of C. difficile. In contrast, in vitro study has shown that fidaxomicin has negligible activity against B. fragilis. The persistent disruption of healthy colonic flora may be the reason for recurrences following a course of treatment with metronidazole or vancomycin. Fidaxomicin has shown to reduce recurrences by approximately 50% when compared to oral vancomycin for primary or 1st episode of recurrent CDI. Determining the efficacy and safety of 30-day duration of fidaxomicin for recurrent CDI through an open label clinical trial has important implications for policy making related to the drug reimbursement programs. In addition, the results of this study will be instrumental in demonstrating to the scientific and healthcare communities there may be a role for the 30-day course of fidaxomicin as a treatment modality for recurrent CDI. Curing CDI will restore the health and quality of life not just at the individual patient level but to the healthcare communities as well. Patients with refractory CDI require prolonged hospital admission, which increases the organism burden within the healthcare facilities. This in turn leads to the spread of the infection to other vulnerable patients. If a 30-day course of fidaxomicin proves to be safe and effective in curing patients with recurrent CDI, it will reduce the risk of severe complications in each patient and reduce transmission of CDI to other susceptible patients.
Interventions
DRUGFidaxomicin
200mg twice daily for 10 days followed by 200mg once daily for 20 days to prevent future recurrence of CDI
Sponsors
McMaster University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years or older. 2. Able to provide informed consent. 3. Willing and able to comply with all the required study procedures. 4. A positive stool test for C. difficile toxin/gene using either PCR or enzyme immunoassay within 3 months of recruitment. 5. History of at least ≥ 2 recurrent CDI within 6 months where recurrence is defined as return of diarrhea consistent with CDI within 8 weeks following CDI symptom resolution for at least 24 hours after a minimum of 10-day course of standard antibiotic therapy and positive stool test for C. difficile toxin or toxin gene and/or ongoing symptoms consistent with CDI despite at least 5 days of treatment using oral vancomycin. 6. Has more than three unformed bowel movements or 200 mL of stool for individuals with a stool collection device such as rectal tube or colostomy during a 24-hour period at the time of initiation of fidaxomicin. Participants will be enrolled when they meet inclusion criteria 1 - 5; will be initiated at fidaxomicin when they have CDI symptoms and stool will be tested for C. difficile toxin/gene. Only those with positive stool for C. difficile toxin/gene with current episode of CDI will continue with the study 7. Females of child bearing potential must be willing to use acceptable birth control as per the Health Canada Guidance Document: Considerations for Inclusion of Women in Clinical Trials and Analysis of Sex Differences.
Exclusion criteria
1. Planned or actively taking an investigational product for another study. 2. Prior fidaxomicin use. 3. Hypersensitivity to fidaxomicin or to any ingredient in the formulation or component of the container. 4. Evidence of toxic megacolon or gastrointestinal perforation on abdominal x-ray or life expectancy of less than 72 hours. 5. Active gastroenteritis due to Salmonella, Shigella, shiga toxin-producing E. coli, Yersinia or Campylobacter. 6. Anticipated requirement for systemic antibiotic therapy for more than 7 days during the study period. 7. Actively taking Saccharomyces boulardii or other probiotics other than yogurt. 8. Any condition that, in the opinion of the investigator, that the treatment may pose a health risk to the subject. 9. Pregnant or lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response at 30-day Completion of Fidaxomicin | 30 days | clinical response will be defined as those participants who have improvement in the number of bowel movements as determined by ≤ 3 unformed stools in a 24-hour period for 2 consecutive days during treatment and remaining well through study day 30. |
| Sustained Clinical Response 8 Weeks Following Completion of 30-day Course of Fidaxomicin | 8 week following completion of fidaxomicin | sustained clinical response will be defined as those participants who have improvement in the number of bowel movements as determined by ≤ 3 unformed stools in a 24-hour period for 2 consecutive days during treatment and remaining well 8 weeks following completion of fidaxomicin |
| Treatment Failure | Up to 8 weeks following completion of fidaxomicin | patients not meeting the definition of cure and requiring additional antibiotics for current CDI episode |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fidaxomicin 30-day fidaxomicin | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
Baseline characteristics
| Characteristic | Fidaxomicin | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 20 Participants | — |
| Age, Categorical Between 18 and 65 years | 11 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Canada | 31 participants | — |
| Sex: Female, Male Female | 23 Participants | — |
| Sex: Female, Male Male | 8 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 29 |
| other Total, other adverse events | 7 / 29 |
| serious Total, serious adverse events | 2 / 29 |
Outcome results
Primary
Clinical Response at 30-day Completion of Fidaxomicin
clinical response will be defined as those participants who have improvement in the number of bowel movements as determined by ≤ 3 unformed stools in a 24-hour period for 2 consecutive days during treatment and remaining well through study day 30.
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fidaxomicin | Clinical Response at 30-day Completion of Fidaxomicin | 24 Participants |
Primary
Sustained Clinical Response 8 Weeks Following Completion of 30-day Course of Fidaxomicin
sustained clinical response will be defined as those participants who have improvement in the number of bowel movements as determined by ≤ 3 unformed stools in a 24-hour period for 2 consecutive days during treatment and remaining well 8 weeks following completion of fidaxomicin
Time frame: 8 week following completion of fidaxomicin
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fidaxomicin | Sustained Clinical Response 8 Weeks Following Completion of 30-day Course of Fidaxomicin | 22 Participants |
Primary
Treatment Failure
patients not meeting the definition of cure and requiring additional antibiotics for current CDI episode
Time frame: Up to 8 weeks following completion of fidaxomicin
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fidaxomicin | Treatment Failure | 7 Participants |