FMT Versus Antimicrobials for Initial Treatment of Recurrent CDI

Study Overview
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Brief Summary
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The purpose of the study is to determine the safety and efficacy of Fecal Microbiota Transplant (FMT) for the treatment of the recurrence of Clostridium difficile infection (CDI) as compared to standard antibiotic therapy. Patients who have tested positive for CDI within 90 days of an admission for relapse of CDI will be approached to participate in this open-label, randomized controlled trial. Patients will either be randomized to the intervention group (receive FMT via retention enema) or the control group (receive antimicrobials targeting CDI).

Detailed Description
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This trial is an open-label, randomized, controlled trial evaluating the safety and efficacy of fecal microbiota transplantation (FMT) for the treatment of the recurrence of Clostridium difficile infection (CDI) as compared to standard antibiotic therapy. Clostridium difficile infection (CDI) has increased in incidence and severity over the last decade and is associated with poor outcomes including increased morbidity, mortality, and healthcare costs (1-8). Relapse occurs in 15-35% of patients after the first episode of CDI and 45-65% of patients who have one relapse will experience a subsequent relapse (9, 10). Dysbiosis - decreased diversity of the fecal microbiome - is thought to contribute to the high rate of relapse (11). FMT quickly and successfully restores normal intestinal microorganisms of the diseased patient via infusion of a liquid stool preparation from a healthy donor. FMT resulted in disease resolution in  90% of cases reported in a systematic review and meta-analyses without any significant adverse events noted (12, 13). All hospitalized patients in the NorthShore system >18 years of age who are diagnosed with active CDI, defined as >3 diarrheal stools per day and a positive C. difficile polymerase chain reaction (PCR) assay, will be evaluated for inclusion in the study. Hospitalized patients presenting with their first or greater relapse of CDI occurring between 15 and 90 days after an index episode of CDI will be eligible for enrollment. Exclusion criteria will include pregnancy, neutropenia (absolute neutrophil count <1000/μl), contraindication for retention enema, or food allergy not controlled for in the donor diet. Eligible patients will undergo written informed consent followed by randomization into intervention and control groups. Patients who are randomized to the intervention group will have antimicrobials targeting C. difficile discontinued at least 6 hours prior to undergoing an FMT via retention enema. A second FMT via retention enema will be administered at 24 hours if diarrhea persists. Patients randomized to the control group will be treated with antimicrobials targeting C. difficile according to the Society for Healthcare Epidemiology of America Clinical Practice Guidelines for CDI (18). FMT will be offered to the control group after 90 days if they experience relapsing CDI. Two healthy universal donors who have previously donated fecal material for FMT have expressed willingness to participate in the study. Donors will complete the American Association of Blood Banks donor questionnaire for exposure to infectious agents as well as undergo serologic and stool testing for communicable diseases or pathogenic bacteria/viruses as previously described (17).

Official Title
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Fecal Microbiota Transplantation Versus Standard Medical Therapy for Initial Treatment of Recurrent Clostridium Difficile Infection

Conditions
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Clostridium Difficile Infection

Intervention / Treatment
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* Biological: FMT
* Drug: Antimicrobials


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of active C. difficile infection, defined as > 3 diarrheal stools per day and a positive C. difficile PCR assay Hospitalized patient presenting with first relapse of CDI occuring between 15 and 90 days after an index episode of CDI Exclusion Criteria: Pregnancy Neutropenia (absolute neutrophil count <1000/microliters) Contraindication for retention enema Food allergy not controlled in the donor diet

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FMT Group (Intervention Arm)<br>Patients randomized to the FMT group will have antimicrobials targeting C. difficile discontinued at least 6 hours prior to undergoing an FMT via retention enema. A second FMT via retention enema will be administered at 24 hours if diarrhea persists. | Biological: FMT<br>* Patients in the FMT group will receive  50 grams of fecal material suspended in bacteriostatic normal saline and glycerol.<br>* Other names: Stool Transplant;|
| Active Comparator: Antimicrobial Group (Control Arm)<br>Patients randomized to the antimicrobial group will be treated with antibiotics targeting C. difficile according to the Society for Healthcare Epidemiology of America (SHEA) Clinical Practice Guidelines for CDI. FMT will be offered to this group after 90 days if they experience relapsing CDI. | Drug: Antimicrobials<br>* Patients randomized to the control group will receive antimicrobials targeting C. difficile.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Clinical Resolution of Diarrhea | Number of patients with resolution of diarrhea and other abdominal symptoms or return to baseline symptoms that were present prior to C. difficile diagnosis | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Clinical Resolution of Symptoms | Amount of time it takes for patient to have cessation of diarrhea and abdominal pain/gastrointestinal symptoms (or return to baseline) and normalization of white blood cell count, creatinine, and temperature. | 90 days | 
| Hospital Length of Stay | Patients' length of stay post-procedure will be measured | 90 days | 
| Number of Patients With Hospital Readmission | Number of patients re-admitted to the hospital for recurrent Clostridium difficile infection | 90 days | 
| Mortality | Number of patients who died from any cause within 90 days of randomization | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CDI, C difficile, C diff, Clostridium difficile