Penn Microbiome Therapy (PMT) for Severe-Clostridium Difficile Infection (CDI)

A Phase II, Randomized Trial to Evaluate the Safety and Efficacy of Fecal Microbiota Transplantation Using the Penn Microbiome Therapy Products for Severe or Severe-Complicated/Fulminant Clostridium Difficile Infection

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).

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