FMT Versus Antimicrobials for Initial Treatment of Recurrent CDI

Sponsor

NorthShore University HealthSystem (Other)

Overall Status

Unknown status

CT.gov ID

NCT02255305

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Clostridium Difficile Infection	Biological: FMT Drug: Antimicrobials	Phase 2

Detailed Description

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2015

Anticipated Primary Completion Date :

Sep 1, 2019

Anticipated Study Completion Date :

Dec 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FMT Group (Intervention Arm) 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 Patients in the FMT group will receive ~50 grams of fecal material suspended in bacteriostatic normal saline and glycerol. Other Names: Fecal Microbiota Transplant Stool Transplant
Active Comparator: Antimicrobial Group (Control Arm) 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 Patients randomized to the control group will receive antimicrobials targeting C. difficile.

Arm

Intervention/Treatment

Experimental: FMT Group (Intervention Arm)

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

Patients in the FMT group will receive ~50 grams of fecal material suspended in bacteriostatic normal saline and glycerol.

Other Names:

Fecal Microbiota Transplant

Stool Transplant

Active Comparator: Antimicrobial Group (Control Arm)

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

Patients randomized to the control group will receive antimicrobials targeting C. difficile.

Outcome Measures

Primary Outcome Measures

Clinical Resolution of Diarrhea [90 days]
Patients will be followed after their procedure to assess for adverse symptoms and relapse of C. difficile infection. Patients will be visited daily during their hospital stay; patients will complete a telephone follow-up call 1 week post-procedure; and patients will complete a clinic visit at 30 days. At the 30-day clinic visit, patients will submit a stool sample to complete C. difficile PCR testing as well as co-colonization of the gastrointestinal tract with multidrug-resistant organisms. Patients will complete a telephone follow up at 3 months and 6 months.

Secondary Outcome Measures

Time to Clinical Resolution of Symptoms [6 months]
Patients will be monitored after the procedure to assess number of daily bowel movements, presence/absence of abdominal pain, white blood cell count, creatinine, and temperature.
Hospital Length of Stay [1 week]
Patients' length of stay post-procedure will be measured. In addition, whether patients were admitted through the ICU and their length of stay in the ICU will be measured.
Readmission and Mortality [90 days]
Patients' readmission for recurrent Clostridium difficile infection will be measured. In addition, patient mortality will be assessed at 90 days post-procedure.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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