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

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

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.

Study Overview

• Status: Terminated
• Conditions: Clostridium Difficile
• Intervention / Treatment: Drug: Bezlotoxumab

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 58 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bezlotoxumab Arm; Single dose of Bezlotoxumab 10mg/kg iv over 60 minutes on Day 0	Drug: Bezlotoxumab; Injection: 1,000 mg/40 mL (25 mg/mL) solution in a single-dose vial.; Other Names: Zinplava
No Intervention: No Bezlotoxumab; 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?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Paul Riska, MD, Montefiore Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2019
• Primary Completion (Actual): May 15, 2022
• Study Completion (Actual): May 15, 2022

Study Registration Dates

• First Submitted: May 2, 2019
• First Submitted That Met QC Criteria: May 2, 2019
• First Posted (Actual): May 6, 2019

Study Record Updates

• Last Update Posted (Actual): November 9, 2022
• Last Update Submitted That Met QC Criteria: October 13, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: diarrhea; clostridium difficile
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Clostridium Infections
• Other Study ID Numbers: 2019-10212

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes