Fecal Microbiota Transplant (FMT) Plus Fidaxomicin for Severe or Fulminant Clostridium Difficile Infection

Clostridium Difficile Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03760484
• Other study ID #: Pro00081229
• Status: Terminated
• Phase: Phase 2
• Start date: January 21, 2019
• Est. completion date: March 10, 2020

Study information

• Verified date: October 2022
• Source: University of Alberta
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: March 10, 2020
• Est. primary completion date: March 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Clostridium Difficile
• Clostridium Infections

Intervention

Drug:
• 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.

Biological:
• 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

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta

Sponsors (1)

Lead Sponsor	Collaborator
University of Alberta

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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)	2 weeks after final Fecal Microbiota Transplant (FMT)
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)	8 weeks after final Fecal Microbiota Transplant (FMT)
Secondary	Death	Reported death	8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days
Secondary	Perforation	Colonic perforation	8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days
Secondary	Infection	Proven infection related final Fecal Microbiota Transplant (FMT)	8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days.
Secondary	Hospitalization	Hospitalization due to C. difficile infection (CDI)	8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days.
Secondary	Colectomy	Surgical Intervention - Colectomy	8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days.