Recurrent Clostridium Difficile Infection
Conditions
Brief summary
The primary goal is to study participants with recurrent C. difficile infection (CDI) treated with lyophilized fecal microbiota transplantation (FMT). The safety, clinical response and relapse rate in patients will be assessed.
Detailed description
Recurrence of CDI following a course of standard antibiotic therapy is high, especially in the elderly patients over 65 years of age, in hospitalized and in the immunocompromised patients. As CDI is characterized by intestinal dysbiosis. Fecal Microbiology Transplantation (FMT) has been investigated as alternative treatment for CDI and has been determined to be effective and safe. One of the major challenges of offering FMT is the availability of suitable donors. A donor may no longer be able to continue to donate for a number of reasons and this may lead to temporary interruption of FMT in centers which offer the program. In order to continue to offer FMT whenever needed, we will investigate the efficacy of lyophilized FMT. The lyophilization (freeze-drying) process works by dehydrating a frozen donor stool sample to complete dryness, using controlled temperature and pressure gradients. This lyophilized process results in a powdered form of the sample. Studies have shown that lyophilized donor stool samples have similar microbial compositions as the same fresh sample.The technique of freeze drying has been used for decades for the industrial storage of microbes and has been used. Preliminary study of lyophilized stool for FMT has been performed in dogs. Preliminary efficacy data in dogs with inflammatory bowel disease suggest equal efficacy as compared to fresh stool, although controlled study has yet to be performed. Should the lyophilized FMT (L-FMT) demonstrate to be equally or more effective than frozen FMT, there would be significant advantages. As with frozen FMT, lyophilized FMT will allow patients to receive FMT immediately as it can take up to two weeks for a donor's screening laboratory testing results to be available. Lyophilized FMT will also be more cost effective as less number of donors will need to be screened given the prolonged shelf life of lyophilized FMT which can be kept at above the freezing temperature. 9 This will also allow wider distribution and accessibility especially to the regions with limited capacity to manufacture FMT.
Interventions
DRUGLyophilized Fecal Microbiota Transplantation
Lyophilized FMT
Sponsors
Vancouver Island Health Authority
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 12 years or older. * Able to provide informed consent. * Willing and able to comply with all the required study procedures. * A positive stool test for C. difficile toxin/gene using either PCR or enzyme immunoassay within 3 months of recruitment unless patient taking treatment specifically for CDI for more than 3 months. * History of at least ≥ 2 recurrent CDI 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 for each episode and/or ongoing symptoms consistent with CDI\* (defined below) despite at least 7 days of treatment using oral vancomycin at a minimum dose of 250 mg four times daily. * Symptoms of CDI include: diarrhea defined as: 3 or more unformed bowel movements in 24 hours for a minimum of 2 days with no other causes for diarrhea
Exclusion criteria
* Planned or actively taking another investigational product * CDI symptom-free for 3 or more weeks following completion of CDI treatment * Patients with neutropenia with absolute neutrophil count \<0.5 x 109/L * Evidence of toxic megacolon or gastrointestinal perforation on abdominal x-ray * Active gastroenteritis due to Salmonella, Shigella, shiga toxin-producing E. coli, Yersinia or Campylobacter. * Presence of colostomy * Unable to tolerate FMT or enema for any reason. * Requiring systemic antibiotic therapy for more than 7 days. * Actively taking Saccharomyces boulardii or other probiotic; yogurt is allowed * Severe underlying disease such that the patient is not expected to survive for at least 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| No Recurrence of CDI-related Diarrhea at 13 Weeks From Last LYO-FMT | 13 weeks from last FMT | No recurrence of CDI-related diarrhea at 13 weeks following last FMT without the need for an intervention antibiotics or additional FMT specifically for CDI recurrence. |
Countries
Canada
Participant flow
Pre-assignment details
Participants must have laboratory or pathology-confirmed diagnosis of recurrent CDI based on Society for Healthcare epidemiology of America SHEA definition, recurrence defined as return of diarrhea and positive stool test after period of symptom resolution within 8 weeks of the first episode and has received at least 10-day oral course of Vancomycin Eligible participants at time of screening will discontinue antibiotic 24-48 hours prior to scheduled FMT
Participants by arm
| Arm | Count |
|---|---|
| Open Label Lyophilized Fecal Microbiota Transplantation Eligible participants with history of recurrent or refractory CDI
Lyophilized Fecal Microbiota Transplantation: Lyophilized FMT | 158 |
| Total | 158 |
Baseline characteristics
| Characteristic | Open Label Lyophilized Fecal Microbiota Transplantation | — |
|---|---|---|
| Age, Continuous | 70.25 years STANDARD_DEVIATION 17.27 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 97 Participants | — |
| Sex: Female, Male Male | 61 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 10 / 158 |
| other Total, other adverse events | 15 / 158 |
| serious Total, serious adverse events | 14 / 158 |
Outcome results
Primary
No Recurrence of CDI-related Diarrhea at 13 Weeks From Last LYO-FMT
No recurrence of CDI-related diarrhea at 13 weeks following last FMT without the need for an intervention antibiotics or additional FMT specifically for CDI recurrence.
Time frame: 13 weeks from last FMT
Population: 140 included in per-protocol analysis for primary endpoint 18 excluded as died/withdrew before week 13
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label Lyophilized Fecal Microbiota Transplantation | No Recurrence of CDI-related Diarrhea at 13 Weeks From Last LYO-FMT | 106 participants |