Clinical trial NCT03760484: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Clostridium Difficile
Keywords: Fecal microbiota transplantation
Fidaxomicin
Lead sponsor: University of Alberta
Sponsor class: OTHER
First posted: 2018-11-30
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: C Difficile Infection (CDI) Resolution- Short Term (Two Weeks After Final Fecal Microbiota Transplant (FMT))
timeFrame: 2 weeks after final Fecal Microbiota Transplant (FMT)
Secondary outcomes:
measure: Sustained C Difficile Infection (CDI) Resolution (Eight Weeks After Final After Final Fecal Microbiota Transplant (FMT))
timeFrame: 8 weeks after final Fecal Microbiota Transplant (FMT)
measure: Death
timeFrame: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days
measure: Perforation
timeFrame: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days
measure: Infection
timeFrame: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days.
measure: Hospitalization
timeFrame: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days.
measure: Colectomy
timeFrame: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days.
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
Study officials:
affiliation: University of Alberta
name: Dina Kao, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.