Clinical trial NCT03937999: Bezlotoxumab as Secondary Prophylaxis for C. Difficile in High-risk Hospitalized Patients Exposed to Antibiotics.
Official title: A Pragmatic Trial of Secondary Prophylaxis With Bezlotoxumab to Prevent C. Difficile Relapse Among Hospitalized Adults Receiving Antibiotics.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Clostridium Difficile
Keywords: clostridium difficile
diarrhea
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2019-05-06
Enrollment: 1
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Intervention group compared to concurrent and historical control groups
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Recurrence of C.Difficile Infection
timeFrame: within 4 weeks
Secondary outcomes:
measure: Recurrence of C.Difficile Infection
timeFrame: within 8 weeks
measure: Rate of Deaths
timeFrame: within 8 weeks
measure: Relapse of C. Difficile by 8 Weeks
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
Study officials:
affiliation: Montefiore Medical Center
name: Paul Riska, MD
role: PRINCIPAL_INVESTIGATOR
References: