Penn Microbiome Therapy (PMT) for Severe-Clostridium Difficile Infection (CDI)
Condition: Severe Clostridium Difficile Infection; Severe-Complicated/Fulminant Clostridium Difficile Infection
MeSH terms: Infections; Communicable Diseases; Clostridium Infections
Intervention: Penn Microbiome Therapy - 001; Penn Microbiome Therapy - 002; Penn Microbiome Therapy - 003; Antibiotics
Intervention description: Fecal Microbiota for Transplant, enema product; Fecal Microbiota for Transplant, suspension product; Fecal Microbiota for Transplant, capsule product; Standard of care antibiotics
Intervention MeSH terms: Anti-Bacterial Agents
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, open label, comparative
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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).
    

Eligibility criteria:

        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