Bezlotoxumab as Secondary Prophylaxis for C. Difficile in High-risk Hospitalized Patients Exposed to Antibiotics.

Study Overview
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Brief Summary
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This study will examine whether the human monoclonal antibody, bezlotoxumab administered AFTER acute Clostridioides difficile (C.diff) has resolved, but during a period of subsequent antibiotic therapy, will eliminate the high risk of C. diff relapse.

Detailed Description
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Clostridioides difficile (C. diff) is a germ (bacteria) that causes life-threatening diarrhea. It is usually a side-effect of taking antibiotics that affect the normal balance of bacteria in the intestines. When the good bacteria in the intestine are killed by antibiotics, the C.diff bacteria begin to grow and produce toxins, causing frequent diarrhea and other symptoms such as abdominal pain or tenderness, loss of appetite, low-grade fever, nausea and vomiting. C. diff can be treated by using special antibiotics, but it tends to come back in about 20% of patients. C-diff is problematic because of frequent relapses after apparent cure. The greatest risk factor for relapse is receipt of subsequent antibiotics, in the hospital, shortly after being treated. Zinplava™(bezlotoxumab) is an FDA approved human monoclonal antibody designed to prevent the recurrence of C.diff.This is not an antibiotic, as it does not kill C. diff, but is an antibody to C. diff toxins, which stops the damage. When Bezlotoxumab is given during a C. diff infection together with antibiotics to kill C. diff, it decreases the risk that C. diff will come back by about one-half. Bezlotoxumab is approved for use when given during a C. diff infection, but it has not been used to prevent C diff in other situations, such as the one being studied in this research.

Official Title
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A Pragmatic Trial of Secondary Prophylaxis With Bezlotoxumab to Prevent C. Difficile Relapse Among Hospitalized Adults Receiving Antibiotics.

Conditions
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Clostridium Difficile

Intervention / Treatment
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* Drug: Bezlotoxumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: C diff diagnosed within 90 days Receipt of high-risk antibiotics for C diff (e.g. Beta-lactams, carbapenems) in an inpatient setting Age 60 years and older Exclusion Criteria: Receipt of current C.diff active antibiotics (oral vancomycin, fidaxomycin, metronidazole, tigecycline/ doxycycline, nitazoxanide, rifamycin) within 72hrs. Not Expected to survive 8 weeks Prior or planned fecal microbiota transplant or Bezlotoxumab use Congestive heart failure (a potential risk of Bezlotoxumab)

Ages Eligible for Study
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Minimum Age: 60 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: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Intervention group compared to concurrent and historical control groups
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bezlotoxumab Arm<br>Single dose of Bezlotoxumab 10mg/kg iv over 60 minutes on Day 0 | Drug: Bezlotoxumab<br>* Injection: 1,000 mg/40 mL (25 mg/mL) solution in a single-dose vial.<br>* Other names: Zinplava;|
| No Intervention: No Bezlotoxumab<br>Control group who are eligible as per the inclusion/exclusion criteria to the Bezlotoxumab arm, but not given Bezlotoxumab (Day 0) . | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of C.Difficile Infection |  | within 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of C.Difficile Infection |  | within 8 weeks | 
| Rate of Deaths |  | within 8 weeks | 
| Relapse of C. Difficile by 8 Weeks |  | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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clostridium difficile, diarrhea