Clostridium Difficile
Conditions
Keywords
clostridium difficile, diarrhea
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.
Interventions
DRUGBezlotoxumab
Injection: 1,000 mg/40 mL (25 mg/mL) solution in a single-dose vial.
Sponsors
Merck Sharp & Dohme LLC
Montefiore Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Intervention group compared to concurrent and historical control groups
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Recurrence of C.Difficile Infection | within 4 weeks |
Secondary
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bezlotoxumab Arm Single dose of Bezlotoxumab 10mg/kg iv over 60 minutes on Day 0
Bezlotoxumab: Injection: 1,000 mg/40 mL (25 mg/mL) solution in a single-dose vial. | 0 |
| No Bezlotoxumab Control group who are eligible as per the inclusion/exclusion criteria to the Bezlotoxumab arm, but not given Bezlotoxumab (Day 0). | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Bezlotoxumab Arm | No Bezlotoxumab | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 1 |
| other Total, other adverse events | 0 / 0 | 0 / 1 |
| serious Total, serious adverse events | 0 / 0 | 0 / 1 |
Outcome results
Primary
Recurrence of C.Difficile Infection
Time frame: within 4 weeks
Population: Only 1 participant was enrolled in the study (into the 'No Bezlotoxumab' control group). No statistical analysis was conducted.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Bezlotoxumab | Recurrence of C.Difficile Infection | 0 Participants |
Secondary
Rate of Deaths
Time frame: within 8 weeks
Population: Only 1 participant was enrolled in the study (into the 'No Bezlotoxumab' control group). No statistical analysis was conducted.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| No Bezlotoxumab | Rate of Deaths | 0 percentage of participants |
Secondary
Recurrence of C.Difficile Infection
Time frame: within 8 weeks
Population: Only 1 participant was enrolled in the study (into the 'No Bezlotoxumab' control group). No statistical analysis was conducted.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Bezlotoxumab | Recurrence of C.Difficile Infection | 0 Participants |
Secondary
Relapse of C. Difficile by 8 Weeks
Time frame: 8 weeks
Population: Only 1 participant was enrolled in the study (into the 'No Bezlotoxumab' control group). No statistical analysis was conducted.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Bezlotoxumab | Relapse of C. Difficile by 8 Weeks | 1 Participants |