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

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

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.

Study Overview

• Status: Terminated
• Conditions: Clostridium Difficile
• Intervention / Treatment: Drug: Fidaxomicin 200 mg; Biological: fecal microbiota transplantation (FMT)

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2X8
      • University of Alberta Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: fecal transplant with fidaxomicin; FMT per rectum x 3 days in conjunction with fidaxomicin (dificid) PO 200 mg bid x 7-10 days	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.; Other Names: dificid; 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; Other Names: biotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Alberta

Publications and helpful links

General Publications

• Monaghan TM, Duggal NA, Rosati E, Griffin R, Hughes J, Roach B, Yang DY, Wang C, Wong K, Saxinger L, Pučić-Baković M, Vučković 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). pii: 3234. doi: 10.3390/cells10113234.

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2019
• Primary Completion (Actual): March 10, 2020
• Study Completion (Actual): March 10, 2020

Study Registration Dates

• First Submitted: November 15, 2018
• First Submitted That Met QC Criteria: November 28, 2018
• First Posted (Actual): November 30, 2018

Study Record Updates

• Last Update Posted (Estimate): December 13, 2022
• Last Update Submitted That Met QC Criteria: November 16, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Fidaxomicin; Fecal microbiota transplantation
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Clostridium Infections; Anti-Infective Agents; Anti-Bacterial Agents; Fidaxomicin
• Other Study ID Numbers: Pro00081229

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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