Fecal Microbiota Transplant (FMT) Plus Fidaxomicin for Severe or Fulminant Clostridium Difficile Infection
Primary Purpose
Clostridium Difficile
Status
Terminated
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Fidaxomicin 200 mg
fecal microbiota transplantation (FMT)
Sponsored by
About this trial
This is an interventional treatment trial for Clostridium Difficile focused on measuring Fecal microbiota transplantation, Fidaxomicin
Eligibility Criteria
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
Sites / Locations
- University of Alberta Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
fecal transplant with fidaxomicin
Arm Description
FMT per rectum x 3 days in conjunction with fidaxomicin (dificid) PO 200 mg bid x 7-10 days
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
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)
Death
Reported death
Perforation
Colonic perforation
Infection
Proven infection related final Fecal Microbiota Transplant (FMT)
Hospitalization
Hospitalization due to C. difficile infection (CDI)
Colectomy
Surgical Intervention - Colectomy
Full Information
NCT ID
NCT03760484
First Posted
November 15, 2018
Last Updated
November 16, 2022
Sponsor
University of Alberta
1. Study Identification
Unique Protocol Identification Number
NCT03760484
Brief Title
Fecal Microbiota Transplant (FMT) Plus Fidaxomicin for Severe or Fulminant Clostridium Difficile Infection
Official Title
Serial Fecal Microbiota Transplant (FMT) Plus Fidaxomicin in the Treatment of Severe or Fulminant Clostridium Difficile Infection, With Detailed Characterization in Microbiota, Metabolomics and Host Immune Response
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Terminated
Why Stopped
Difficulty enrolling participants/COVID pandemic/lack of continued in-kind support from product manufacturer.
Study Start Date
January 21, 2019 (Actual)
Primary Completion Date
March 10, 2020 (Actual)
Study Completion Date
March 10, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Alberta
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clostridium Difficile
Keywords
Fecal microbiota transplantation, Fidaxomicin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
fecal transplant with fidaxomicin
Arm Type
Experimental
Arm Description
FMT per rectum x 3 days in conjunction with fidaxomicin (dificid) PO 200 mg bid x 7-10 days
Intervention Type
Drug
Intervention Name(s)
Fidaxomicin 200 mg
Other Intervention Name(s)
dificid
Intervention Description
Each cycle consists of fidaxomicin 200 mg PO bid x 7-10 days till clinical efficacy is achieved, to a max of 4 cycles.
Intervention Type
Biological
Intervention Name(s)
fecal microbiota transplantation (FMT)
Other Intervention Name(s)
biotherapy
Intervention Description
Each cycle consists of FMT per rectum daily x 3 days till clinical efficacy is achieved to a max of 4 cycles
Primary Outcome Measure Information:
Title
C Difficile Infection (CDI) Resolution- Short Term (Two Weeks After Final Fecal Microbiota Transplant (FMT))
Description
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)
Secondary Outcome Measure Information:
Title
Sustained C Difficile Infection (CDI) Resolution (Eight Weeks After Final After Final Fecal Microbiota Transplant (FMT))
Description
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)
Title
Death
Description
Reported death
Time Frame
8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days
Title
Perforation
Description
Colonic perforation
Time Frame
8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days
Title
Infection
Description
Proven infection related final Fecal Microbiota Transplant (FMT)
Time Frame
8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days.
Title
Hospitalization
Description
Hospitalization due to C. difficile infection (CDI)
Time Frame
8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days.
Title
Colectomy
Description
Surgical Intervention - Colectomy
Time Frame
8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dina Kao, MD
Organizational Affiliation
University of Alberta
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alberta Hospital
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2X8
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34831456
Citation
Monaghan TM, Duggal NA, Rosati E, Griffin R, Hughes J, Roach B, Yang DY, Wang C, Wong K, Saxinger L, Pucic-Bakovic M, Vuckovic F, Klicek F, Lauc G, Tighe P, Mullish BH, Blanco JM, McDonald JAK, Marchesi JR, Xue N, Dottorini T, Acharjee A, Franke A, Li Y, Wong GK, Polytarchou C, Yau TO, Christodoulou N, Hatziapostolou M, Wang M, Russell LA, Kao DH. A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Clostridioides difficile Infection. Cells. 2021 Nov 19;10(11):3234. doi: 10.3390/cells10113234.
Results Reference
background
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Fecal Microbiota Transplant (FMT) Plus Fidaxomicin for Severe or Fulminant Clostridium Difficile Infection
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