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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Clostridium Difficile

Intervention / Treatment
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* Drug: Fidaxomicin 200 mg
* Biological: fecal microbiota transplantation (FMT)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: fecal transplant with fidaxomicin<br>FMT per rectum x 3 days in conjunction with fidaxomicin (dificid) PO 200 mg bid x 7-10 days | Drug: Fidaxomicin 200 mg<br>* Each cycle consists of fidaxomicin 200 mg PO bid x 7-10 days till clinical efficacy is achieved, to a max of 4 cycles.<br>* Other names: dificid;Biological: fecal microbiota transplantation (FMT)<br>* Each cycle consists of FMT per rectum daily x 3 days till clinical efficacy is achieved to a max of 4 cycles<br>* Other names: biotherapy;|

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fecal microbiota transplantation, Fidaxomicin