Inflammatory Bowel Diseases, Clostridium Difficile Infection
Conditions
Keywords
Crohn's DIsease, Ulcerative Colitis
Brief summary
This is a randomized controlled trial to assess the clinical and microbiological impacts of FMT in combination with Bezlotoxumab (bezlo) compared to FMT in combination with placebo in patients with both inflammatory bowel disease (IBD) a and clostridium difficile infection (CDI). The investigators will prospectively enroll up to 150 IBD-CDI patients from 4 tertiary care FMT referral centers. Patients will be randomized 1:1 to either receive FMT in combination with Bezlo of FMT and a placebo infusion. Donor stool from healthy donors will be obtained from OpenBiome. OpenBiome is a nonprofit 501(c)(3) organization that provides hospitals with screened, filtered, and frozen material ready for clinical use. Patients will be enrolled and followed prospectively for 3 months post therapy. Stool and blood samples as well as clinical data will be collected at baseline, week 1, 8 and 12.
Interventions
DRUGBezlotoxumab
This is a a fully human monoclonal antibody that binds to C. difficile toxin B, and is indicated to prevent recurrence of CDI in adults at risk for recurrent CDI (rCDI).
DRUGPlacebo
placebo is an infusion of normal saline.
DRUGFecal Microbiota Transplantation
FMT is an infusion of prescreened donor stool that will be administered via colonoscopy
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults age 18 or greater * History of ≥ 2 episodes of recurrent CDI. CDI is defined as the presence of diarrhea ( Bristol 6 or 7 for 48 hours and a confirmatory test for CDI). Preferred testing will be a two-step method using GDH/EIA toxin, though PCR will be accepted based on hospital availability with confirmation of the most recent episode occurring within the prior 3 months * Confirmed diagnosis of IBD (ulcerative colitis, Crohn's disease or indeterminate colitis) * Undergoing FMT via colonoscopy for CDI as part of standard medical care
Exclusion criteria
* Unable or unwilling to undergo a colonoscopy * Inpatient status, though patients can be screened while inpatients, the must be outpatient for the planned colonoscopy. * Anticipated immediate or upcoming surgery within 30 days * Need for continued non-anti-CDI antibiotic therapy * History of total proctocolectomy * Female patients who are pregnant or breastfeeding or plan to become pregnant in the next 6 months. * Patients who are unable to give informed consent * Participation in a clinical trial in the preceding 30 days or simultaneously during this trial * Severe food allergy (anaphylaxis or anaphylactoid-like reaction) * Life expectancy \< 6 months * Unable to adhere to protocol requirements * Patient who have received an FMT in the past year * Any condition that the physician investigators deems unsafe, including other conditions or medications that the investigator determines that it will put the subject at greater risk from FMT * Patient who is diagnosed with NYHA class 3 or 4 Heart Failure * Lab value of WBC \<3.0 x 103/mm3 , Platelets \<100 x 103/mm3 , ALT or AST \> 1.5 x institutional ULN * EBV or CMV negative if a patient is severely immunosuppressed ( defined as 3 or more immunosuppressing agents)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clostridium Difficile Recurrence | 8 weeks | positive test for CDI by EIA toxin |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FMT + Bezlo Participants received an FMT via colonoscopy (250ml) as well as a single IV infusion of bezlotoxumab (10mg/kg) that took place over 60 minutes.
Bezlotoxumab: This is a a fully human monoclonal antibody that binds to C. difficile toxin B, and is indicated to prevent recurrence of CDI in adults at risk for recurrent CDI (rCDI).
Fecal Microbiota Transplantation: FMT is an infusion of prescreened donor stool that will be administered via colonoscopy | 30 |
| FMT + Placebo Participants received a single FMT via colonoscopy (250ml) and a placebo (saline) infusion (250cc) over 60 minutes.
Placebo: placebo is an infusion of normal saline.
Fecal Microbiota Transplantation: FMT is an infusion of prescreened donor stool that will be administered via colonoscopy | 31 |
| Total | 61 |
Baseline characteristics
| Characteristic | FMT + Placebo | Total | FMT + Bezlo |
|---|---|---|---|
| Age, Continuous | 34 years | 38 years | 38.5 years |
| Baseline Bowel Movement | 4 bowel movements | 5 bowel movements | 5 bowel movements |
| Baseline Bristol Score | 5 units on a scale | 5 units on a scale | 5 units on a scale |
| Baseline Calprotectin | 241 mcg/g | 635 mcg/g | 930.5 mcg/g |
| Baseline Harvey Bradshaw Index | 6.5 units on a scale | 6.5 units on a scale | 7 units on a scale |
| Baseline Partial Mayo | 2 units on a scale | 3 units on a scale | 3.5 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 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 | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 27 Participants | 54 Participants | 27 Participants |
| Sex: Female, Male Female | 14 Participants | 28 Participants | 14 Participants |
| Sex: Female, Male Male | 17 Participants | 33 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 31 |
| other Total, other adverse events | 16 / 30 | 15 / 31 |
| serious Total, serious adverse events | 5 / 30 | 4 / 31 |
Outcome results
Primary
Number of Participants With Clostridium Difficile Recurrence
positive test for CDI by EIA toxin
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FMT + Bezlo | Number of Participants With Clostridium Difficile Recurrence | 4 Participants |
| FMT + Placebo | Number of Participants With Clostridium Difficile Recurrence | 1 Participants |
p-value: 0.15Wilcoxon (Mann-Whitney)