Recurrent Clostridium Difficile Infection
Conditions
Brief summary
This is a randomized, open label, comparative, Phase II study to determine which dose of fecal microbiota transplant using Penn Microbiome Therapy (PMT) products is most effective in treating and preventing recurrence of Clostridium difficile infection (C diff).
Interventions
Fecal Microbiota for Transplant, enema product
Fecal Microbiota for Transplant, suspension product
Fecal Microbiota for Transplant, capsule product
Sponsors
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized, open label, comparative
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Second or greater episode of CDI (first or greater recurrence) within 12 months, with symptoms including bowel movement altered in frequency or consistency from baseline. 2. Stool positive for C. difficile toxin by EIA or toxin gene by NAAT within 60 days of enrollment. 3. At least one additional prior positive stool test for C. difficile within the prior 12 months (EIA or NAAT as above). 4. Age ≥ 18 years. 5. Minimum of 72 hours of receipt of standard-of-care (vancomycin or fidaxomicin) antibiotic treatment for R-CDI prior to intervention.
Exclusion criteria
1. Evidence of colon/small bowel perforation at the time of study screening 2. Goals of care are directed to comfort rather than curative measures. 3. Moderate (ANC \< 1000 cells/uL) or severe (ANC \< 500 cells/uL) neutropenia. 4. Known food allergy that could lead to anaphylaxis. 5. Pregnancy a. For subjects of childbearing potential (ages 18 to 55), the subject must have a negative urine pregnancy test within 48 hours of consent and no more than 48 hours prior to first product administration 6. Meeting criteria for severe, severe-complicated/fulminant CDI within 24 hours of planned trial enrollment. We define severe or severe-complicated/fulminant CDI as any one of the following: (1) leukocytosis with peripheral WBC ≥ 15,000 cells/mL; (2) hypotension with systolic blood pressure sustained \< 90mmHg for three or more hours or requiring pressors; (3) provider documentation of ileus or radiologic evidence of bowel dilation or megacolon; (4) acute kidney injury with increase in baseline serum creatinine level by ≥50% or new dialysis initiation; (5) serum lactate \> 2.2 mmol/L; or (6) ≥ 3 systemic inflammatory response syndrome (SIRS) criteria (which include heart rate \> 90 beats per minute, respiratory rate \> 20 breaths per minute or PaCO2 \< 32 mmHg, temperature \>38ºC or \<36ºC, WBC \> 12,000 cells/uL, \<4,000 cells/uL, or \>10% immature (band) forms). 7. Receipt of FMT or enrollment in a clinical trial for FMT within the last 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Resolution of Symptoms After Treatment With One of the PMT Suite of Products or Control. | 8 weeks | Clinical resolution will be compared by determining the proportion of subjects with clinical resolution of diarrhea without recurrence in subjects with R-CDI at 8 weeks (56 days) following FMT. Clinical resolution will be defined as follows: * ≤ 4 stools per calendar day for the prior two days with no stool of Bristol stool scale type 7 * No additional stool tests with a positive EIA for C. difficile toxin since study enrollment * No additional prescription or use of anti-CDI antibiotics (unless given for prophylaxis) since study enrollment * No need for an additional |
Secondary
| Measure | Time frame |
|---|---|
| All-cause Mortality at 60-days Following Last FMT | 60 days |
| Colectomy or Diverting Ileostomy Within 30 Days After Last FMT | 30 days |
| Cumulative Days of Hospitalization From Enrollment Until 30 Days After FMT | 30 days |
| All-cause Mortality at 30-days Following Last FMT | 30 days |
| Bacteremia From Enrollment Until 30 Days After Last FMT | 30 days |
| Hospital Admission Within 60 Days of Discharge From Index Hospitalization | 60 days |
| Cumulative Days in Intensive Care Unit From Enrollment Until 30 Days After Last FMT | 30 Days |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Dose of PMT Penn Microbiome Therapy - 001: Fecal Microbiota for Transplant, enema product
Penn Microbiome Therapy - 002: Fecal Microbiota for Transplant, suspension product
Penn Microbiome Therapy - 003: Fecal Microbiota for Transplant, capsule product | 5 |
| Two Doses of PMT Administered within 24 hours
Penn Microbiome Therapy - 001: Fecal Microbiota for Transplant, enema product
Penn Microbiome Therapy - 002: Fecal Microbiota for Transplant, suspension product
Penn Microbiome Therapy - 003: Fecal Microbiota for Transplant, capsule product | 4 |
| Total | 9 |
Baseline characteristics
| Characteristic | Single Dose of PMT | Two Doses of PMT | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 3 Participants | 5 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 | 3 Participants | 2 Participants | 5 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment United States | 5 participants | 4 participants | 9 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 4 |
| other Total, other adverse events | 5 / 5 | 4 / 4 |
| serious Total, serious adverse events | 3 / 5 | 3 / 4 |
Outcome results
Primary
Number of Subjects With Resolution of Symptoms After Treatment With One of the PMT Suite of Products or Control.
Clinical resolution will be compared by determining the proportion of subjects with clinical resolution of diarrhea without recurrence in subjects with R-CDI at 8 weeks (56 days) following FMT. Clinical resolution will be defined as follows: * ≤ 4 stools per calendar day for the prior two days with no stool of Bristol stool scale type 7 * No additional stool tests with a positive EIA for C. difficile toxin since study enrollment * No additional prescription or use of anti-CDI antibiotics (unless given for prophylaxis) since study enrollment * No need for an additional
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Dose of PMT | Number of Subjects With Resolution of Symptoms After Treatment With One of the PMT Suite of Products or Control. | 1 Participants |
| Two Doses of PMT | Number of Subjects With Resolution of Symptoms After Treatment With One of the PMT Suite of Products or Control. | 2 Participants |
Secondary
All-cause Mortality at 30-days Following Last FMT
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Dose of PMT | All-cause Mortality at 30-days Following Last FMT | 0 Participants |
| Two Doses of PMT | All-cause Mortality at 30-days Following Last FMT | 0 Participants |
Secondary
All-cause Mortality at 60-days Following Last FMT
Time frame: 60 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Dose of PMT | All-cause Mortality at 60-days Following Last FMT | 0 Participants |
| Two Doses of PMT | All-cause Mortality at 60-days Following Last FMT | 0 Participants |
Secondary
Bacteremia From Enrollment Until 30 Days After Last FMT
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Dose of PMT | Bacteremia From Enrollment Until 30 Days After Last FMT | 1 Participants |
| Two Doses of PMT | Bacteremia From Enrollment Until 30 Days After Last FMT | 0 Participants |
Secondary
Colectomy or Diverting Ileostomy Within 30 Days After Last FMT
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Dose of PMT | Colectomy or Diverting Ileostomy Within 30 Days After Last FMT | 0 Participants |
| Two Doses of PMT | Colectomy or Diverting Ileostomy Within 30 Days After Last FMT | 0 Participants |
Secondary
Cumulative Days in Intensive Care Unit From Enrollment Until 30 Days After Last FMT
Time frame: 30 Days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Single Dose of PMT | Cumulative Days in Intensive Care Unit From Enrollment Until 30 Days After Last FMT | 0 days |
| Two Doses of PMT | Cumulative Days in Intensive Care Unit From Enrollment Until 30 Days After Last FMT | 0 days |
Secondary
Cumulative Days of Hospitalization From Enrollment Until 30 Days After FMT
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Single Dose of PMT | Cumulative Days of Hospitalization From Enrollment Until 30 Days After FMT | 10 days |
| Two Doses of PMT | Cumulative Days of Hospitalization From Enrollment Until 30 Days After FMT | 1 days |
Secondary
Hospital Admission Within 60 Days of Discharge From Index Hospitalization
Time frame: 60 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Dose of PMT | Hospital Admission Within 60 Days of Discharge From Index Hospitalization | 3 Participants |
| Two Doses of PMT | Hospital Admission Within 60 Days of Discharge From Index Hospitalization | 1 Participants |