Clostridium Difficile
Conditions
Keywords
Fecal microbiota transplantation, Fidaxomicin
Brief summary
Fecal microbiota transplantation (FMT) has been very effective for patients who suffer from mild C diff infection (CDI) which recurs but it is unclear how effective FMT alone is in treating severe and fulminant CDI. Current evidence suggests that FMT in combination with vancomycin is required, and that multiple treatments are necessary. The investigators think fidaxomicin may be a better option in the context and may potentially reduce the number of FMT required. However, fidaxomicin has never been used to treat severe or fulminant CDI. In this pilot study, the investigators plan to use a combination of FMT plus fidaxomicin to determine efficacy and safety in treating patients with severe or fulminant CDI. The investigators want to see if this approach may reduce the number of FMT treatment required, and/or the length of hospital stay.
Detailed description
In this prospective, open -label, multi--center feasibility study, the investigators aim to determine the efficacy and safety of using combined serial FMT by enema plus fidaxomicin to treat patients who have severe or fulminant CDI not responding to maximal medical therapy. The hypothesis is the combination of FMT plus fidaxomicin can reduce the number of FMT required and/or hospital length of stay compared to FMT plus vancomycin. Participants will receive FMT by enemas over 3 days which constitutes a single cycle with concurrent treatment with oral fidaxomicin. If participants do not show improvement biochemically or clinically, then a repeat FMT cycle will be administered to a maximum of 4 cycles.
Interventions
Each cycle consists of fidaxomicin 200 mg PO bid x 7-10 days till clinical efficacy is achieved, to a max of 4 cycles.
BIOLOGICALfecal microbiota transplantation (FMT)
Each cycle consists of FMT per rectum daily x 3 days till clinical efficacy is achieved to a max of 4 cycles
Sponsors
University of Alberta
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
* Age \> 18 years with severe1 or fulminant2 CDI, without an adequate response to metronidazole IV 500 mg q8H and vancomycin 500 mg PO q6h for at least 2 days or after Fecal Microbiota Transplant (FMT). An adequate response is defined as a decrease in stool frequency or inflammatory markers (WBC or C reactive protein) by 10% over 48 hours * Those with ability to provide informed consent or an alternative decision maker providing assent
Exclusion criteria
* Those with bowel perforation * Those taking chemotherapy or radiation treatment with absolute neutrophil count of \< 1000 cells/mm3 * Those with known colonic strictures * Those with subtotal colectomy or planning to have a colectomy * Those with significant ileus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| C Difficile Infection (CDI) Resolution- Short Term (Two Weeks After Final Fecal Microbiota Transplant (FMT)) | 2 weeks after final Fecal Microbiota Transplant (FMT) | Defined as \<3 unformed bowel movements/24h or return to baseline bowel habit 2 weeks after final Fecal Microbiota Transplant (FMT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Death | 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days | Reported death |
| Perforation | 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days | Colonic perforation |
| Sustained C Difficile Infection (CDI) Resolution (Eight Weeks After Final After Final Fecal Microbiota Transplant (FMT)) | 8 weeks after final Fecal Microbiota Transplant (FMT) | Sustained C difficile infection (CDI) resolution defined as lack of C difficile infection (CDI) recurrence 8 weeks after final Fecal Microbiota Transplant (FMT) |
| Hospitalization | 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days. | Hospitalization due to C. difficile infection (CDI) |
| Colectomy | 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days. | Surgical Intervention - Colectomy |
| Infection | 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days. | Proven infection related final Fecal Microbiota Transplant (FMT) |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fecal Transplant With Fidaxomicin FMT per rectum x 3 days in conjunction with fidaxomicin (dificid) PO 200 mg bid x 7-10 days
Fidaxomicin 200 mg: Each cycle consists of fidaxomicin 200 mg PO bid x 7-10 days till clinical efficacy is achieved, to a max of 4 cycles.
Fecal Microbiota Transplantation (FMT): Each cycle consists of FMT per rectum daily x 3 days till clinical efficacy is achieved to a max of 4 cycles | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Fecal Transplant With Fidaxomicin |
|---|---|
| Age, Customized 60-69 years | 1 Participants |
| Age, Customized 70-79 years | 1 Participants |
| Age, Customized 80+ years | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment Canada | 4 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
C Difficile Infection (CDI) Resolution- Short Term (Two Weeks After Final Fecal Microbiota Transplant (FMT))
Defined as \<3 unformed bowel movements/24h or return to baseline bowel habit 2 weeks after final Fecal Microbiota Transplant (FMT)
Time frame: 2 weeks after final Fecal Microbiota Transplant (FMT)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fecal Transplant With Fidaxomicin | C Difficile Infection (CDI) Resolution- Short Term (Two Weeks After Final Fecal Microbiota Transplant (FMT)) | 4 Participants |
Secondary
Colectomy
Surgical Intervention - Colectomy
Time frame: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fecal Transplant With Fidaxomicin | Colectomy | 0 Participants |
Secondary
Death
Reported death
Time frame: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fecal Transplant With Fidaxomicin | Death | 0 Participants |
Secondary
Hospitalization
Hospitalization due to C. difficile infection (CDI)
Time frame: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fecal Transplant With Fidaxomicin | Hospitalization | 0 Participants |
Secondary
Infection
Proven infection related final Fecal Microbiota Transplant (FMT)
Time frame: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fecal Transplant With Fidaxomicin | Infection | 0 Participants |
Secondary
Perforation
Colonic perforation
Time frame: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fecal Transplant With Fidaxomicin | Perforation | 0 Participants |
Secondary
Sustained C Difficile Infection (CDI) Resolution (Eight Weeks After Final After Final Fecal Microbiota Transplant (FMT))
Sustained C difficile infection (CDI) resolution defined as lack of C difficile infection (CDI) recurrence 8 weeks after final Fecal Microbiota Transplant (FMT)
Time frame: 8 weeks after final Fecal Microbiota Transplant (FMT)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fecal Transplant With Fidaxomicin | Sustained C Difficile Infection (CDI) Resolution (Eight Weeks After Final After Final Fecal Microbiota Transplant (FMT)) | 3 Participants |