Severe Clostridium Difficile Infection, Severe-Complicated/Fulminant Clostridium Difficile Infection
Conditions
Brief summary
This is a randomized, open label, comparative, Phase II study to determine whether fecal microbiota transplant using Penn Microbiome Therapy products helps standard therapy to treat severe Clostridium difficile infection (C diff).
Interventions
Fecal Microbiota for Transplant, enema product
Fecal Microbiota for Transplant, suspension product
Fecal Microbiota for Transplant, capsule product
DRUGAntibiotics
Standard of care antibiotics
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\. One or more episodes of CDI with symptoms including bowel movements altered in frequency or consistency from baseline. * 2\. Stool test positive for Clostridium difficile by enzyme immunoassay (EIA) by FDA-cleared assay within 7 days prior to enrollment. * 3\. Age ≥ 18 years * 4\. Meets any one of the listed criteria for severe or severe-complicated/fulminant disease within 72 hours of enrollment. * 5\. Receiving antibiotic treatment for S/SC(Severe-complicatedcategory)/F-CDI per current Infectious Diseases Society of America(IDSA) guidelines. Enrollment criteria details: * 1\. Must either meet ≥1 criteria in severe category or in severe complicated category to be enrolled * 2\. If the subject meets criteria in both categories, stratify to the higher severity category (severe complicated) * 3\. Detailed enrollment criteria definitions: * a. white blood cells (WBC) ≥15,000 cells/uL - if any value in the time period meets this definition * b. Hypotension with systolic blood pressure sustained \< 90mmHg for three or more hours or requiring vasopressors (epinephrine, norepinephrine, phenylephrine, or vasopressin) * c. Acute kidney injury - increase in serum creatinine level by ≥50% or new dialysis initiation * i. If a baseline serum creatinine value is not available, acute kidney injury will be defined as a serum creatinine \>1.5 mg/dL * d. Temperature ≥38.5 °C or \<35.6°C - one value needed in time period - * e. Ileus, bowel dilation or megacolon * i. Ileus: If noted in any provider documentation or problem list (search words ileus) OR * ii. If the words dilated dilation or ileus are noted in a radiology report on intestines/colon, or if megacolon noted * f. Lactate \>2.2 mmol/L - if any value in the time period meets this definition * g. Systemic inflammatory response syndrome(SIRS) criteria * i. Heart rate \> 90 beats per minute * ii. Respiratory rate \> 20 breaths per minute or PaCO2 \< 32 mmHg * iii. Temperature \>38ºC or \<36ºC * iv. WBC \> 12,000 cells/uL, \<4,000 cells/uL, or \>10% immature (band) forms
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 Receipt of Fecal Microbiota Transplantation (FMT) or enrollment in a clinical trial for FMT within the last 3 months. * 7 COVID-19 infection, as defined by a positive nucleic acid or antigen test within the prior 14 days and symptoms consistent with COVID-19 infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Resolution of Symptoms After Treatment With One of the PMT Suite of Products. | 3 Days | The outcome will be satisfied when the subject is discharged from the hospital (not to hospice or palliative care) or, while the subject remains hospitalized, when the following criteria are met for 72 hours: * If radiology study or studies performed, ileus/dilation/megacolon either not noted or noted as resolved * Ileus/megacolon either noted as resolved by any provider documentation or not noted * White Blood Cells (WBC) \<15,000 cells/uL * Serum creatinine decreased, unchanged, or increased by ≤0.2 mg/dL over 72 hours (if not receiving continuous renal replacement therapy (CRRT) or hemodialysis (HD)) * Lactate ≤2.2 mmol/L (if measured by clinical care team) * No vasopressors used (including epinephrine, norepinephrine, phenylephrine, or vasopressin) * Temperature \<38.5 °C and ≥35.6°C * \< 8 bowel movements per day and \< 600 mL unformed stool (if volume recorded) * Meeting fewer than 3 systemic inflammatory response syndrome (SIRS) criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Cumulative Days in Intensive Care Unit From Enrollment Until 30 Days After Last FMT | 30 Days | — |
| All-cause Mortality at 60-days Following Last FMT | 60 Days | Number of deaths within 60 days of the last FMT |
| All-cause Mortality at 30 Days Following Last Fecal Microbiota Transplantation (FMT) | 30 Days | Number of deaths within 30 days of the last FMT |
| Repeat Hospital Admission Within 60 Days of Discharge From Index Hospitalization | 60 Days | — |
| Bacteremia From Enrollment Until 30 Days After Last FMT | 30 Days | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| No Investigational Product Participants who receive the antibiotics usually prescribed for C diff infection.
Antibiotics: Standard of care antibiotics | 5 |
| Upper Gastrointestinal Fecal Microbiota Transplantation Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given by mouth in capsules or through a tube that goes into your stomach/intestines if you already have one (upper delivery). You will not be assigned to this group if you cannot take any medications either by mouth or through a tube safely, as determined by your doctor
Penn Microbiome Therapy - 002: Fecal Microbiota for Transplant, suspension product
Penn Microbiome Therapy - 003: Fecal Microbiota for Transplant, capsule product
Antibiotics: Standard of care antibiotics | 4 |
| Lower Gastrointestinal Fecal Microbiota Transplantation Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given through the rectum by an enema (lower delivery).
Penn Microbiome Therapy - 001: Fecal Microbiota for Transplant, enema product
Antibiotics: Standard of care antibiotics | 6 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 2 | 2 | 1 |
| Overall Study | Subject re-enrolled into Upper GI | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | No Investigational Product | Upper Gastrointestinal Fecal Microbiota Transplantation | Lower Gastrointestinal Fecal Microbiota Transplantation | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 4 Participants | 3 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 5 Participants | 10 Participants |
| Region of Enrollment United States | 5 participants | 4 participants | 6 participants | 15 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 5 | 2 / 4 | 1 / 6 |
| other Total, other adverse events | 4 / 5 | 4 / 4 | 6 / 6 |
| serious Total, serious adverse events | 3 / 5 | 3 / 4 | 4 / 6 |
Outcome results
Primary
Number of Subjects With Resolution of Symptoms After Treatment With One of the PMT Suite of Products.
The outcome will be satisfied when the subject is discharged from the hospital (not to hospice or palliative care) or, while the subject remains hospitalized, when the following criteria are met for 72 hours: * If radiology study or studies performed, ileus/dilation/megacolon either not noted or noted as resolved * Ileus/megacolon either noted as resolved by any provider documentation or not noted * White Blood Cells (WBC) \<15,000 cells/uL * Serum creatinine decreased, unchanged, or increased by ≤0.2 mg/dL over 72 hours (if not receiving continuous renal replacement therapy (CRRT) or hemodialysis (HD)) * Lactate ≤2.2 mmol/L (if measured by clinical care team) * No vasopressors used (including epinephrine, norepinephrine, phenylephrine, or vasopressin) * Temperature \<38.5 °C and ≥35.6°C * \< 8 bowel movements per day and \< 600 mL unformed stool (if volume recorded) * Meeting fewer than 3 systemic inflammatory response syndrome (SIRS) criteria
Time frame: 3 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Investigational Product | Number of Subjects With Resolution of Symptoms After Treatment With One of the PMT Suite of Products. | 4 Participants |
| Upper Gastrointestinal Fecal Microbiota Transplantation | Number of Subjects With Resolution of Symptoms After Treatment With One of the PMT Suite of Products. | 3 Participants |
| Lower Gastrointestinal Fecal Microbiota Transplantation | Number of Subjects With Resolution of Symptoms After Treatment With One of the PMT Suite of Products. | 5 Participants |
Secondary
All-cause Mortality at 30 Days Following Last Fecal Microbiota Transplantation (FMT)
Number of deaths within 30 days of the last FMT
Time frame: 30 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Investigational Product | All-cause Mortality at 30 Days Following Last Fecal Microbiota Transplantation (FMT) | 1 Participants |
| Upper Gastrointestinal Fecal Microbiota Transplantation | All-cause Mortality at 30 Days Following Last Fecal Microbiota Transplantation (FMT) | 2 Participants |
| Lower Gastrointestinal Fecal Microbiota Transplantation | All-cause Mortality at 30 Days Following Last Fecal Microbiota Transplantation (FMT) | 1 Participants |
Secondary
All-cause Mortality at 60-days Following Last FMT
Number of deaths within 60 days of the last FMT
Time frame: 60 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Investigational Product | All-cause Mortality at 60-days Following Last FMT | 1 Participants |
| Upper Gastrointestinal Fecal Microbiota Transplantation | All-cause Mortality at 60-days Following Last FMT | 2 Participants |
| Lower Gastrointestinal Fecal Microbiota Transplantation | All-cause Mortality at 60-days Following Last FMT | 1 Participants |
Secondary
Bacteremia From Enrollment Until 30 Days After Last FMT
Time frame: 30 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Investigational Product | Bacteremia From Enrollment Until 30 Days After Last FMT | 0 Participants |
| Upper Gastrointestinal Fecal Microbiota Transplantation | Bacteremia From Enrollment Until 30 Days After Last FMT | 0 Participants |
| Lower Gastrointestinal Fecal Microbiota Transplantation | 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) |
|---|---|---|
| No Investigational Product | Colectomy or Diverting Ileostomy Within 30 Days After Last FMT | 0 Participants |
| Upper Gastrointestinal Fecal Microbiota Transplantation | Colectomy or Diverting Ileostomy Within 30 Days After Last FMT | 0 Participants |
| Lower Gastrointestinal Fecal Microbiota Transplantation | 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) |
|---|---|---|
| No Investigational Product | Cumulative Days in Intensive Care Unit From Enrollment Until 30 Days After Last FMT | 0 days |
| Upper Gastrointestinal Fecal Microbiota Transplantation | Cumulative Days in Intensive Care Unit From Enrollment Until 30 Days After Last FMT | 0 days |
| Lower Gastrointestinal Fecal Microbiota Transplantation | 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) |
|---|---|---|
| No Investigational Product | Cumulative Days of Hospitalization From Enrollment Until 30 Days After FMT | 13 days |
| Upper Gastrointestinal Fecal Microbiota Transplantation | Cumulative Days of Hospitalization From Enrollment Until 30 Days After FMT | 8 days |
| Lower Gastrointestinal Fecal Microbiota Transplantation | Cumulative Days of Hospitalization From Enrollment Until 30 Days After FMT | 14 days |
Secondary
Repeat Hospital Admission Within 60 Days of Discharge From Index Hospitalization
Time frame: 60 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Investigational Product | Repeat Hospital Admission Within 60 Days of Discharge From Index Hospitalization | 2 Participants |
| Upper Gastrointestinal Fecal Microbiota Transplantation | Repeat Hospital Admission Within 60 Days of Discharge From Index Hospitalization | 1 Participants |
| Lower Gastrointestinal Fecal Microbiota Transplantation | Repeat Hospital Admission Within 60 Days of Discharge From Index Hospitalization | 3 Participants |