Clinical trial NCT03970200: Penn Microbiome Therapy (PMT) for Severe-Clostridium Difficile Infection (CDI)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Severe Clostridium Difficile Infection
Severe-Complicated/Fulminant Clostridium Difficile Infection
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2019-05-31
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, open label, comparative
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Number of Subjects With Resolution of Symptoms After Treatment With One of the PMT Suite of Products.
timeFrame: 3 Days
Secondary outcomes:
measure: All-cause Mortality at 30 Days Following Last Fecal Microbiota Transplantation (FMT)
timeFrame: 30 Days
measure: All-cause Mortality at 60-days Following Last FMT
timeFrame: 60 Days
measure: Colectomy or Diverting Ileostomy Within 30 Days After Last FMT
timeFrame: 30 Days
measure: Cumulative Days of Hospitalization From Enrollment Until 30 Days After FMT
timeFrame: 30 Days
measure: Cumulative Days in Intensive Care Unit From Enrollment Until 30 Days After Last FMT
timeFrame: 30 Days
measure: Bacteremia From Enrollment Until 30 Days After Last FMT
timeFrame: 30 Days
measure: Repeat Hospital Admission Within 60 Days of Discharge From Index Hospitalization
timeFrame: 60 Days
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Hospital of the Univeristy of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Division of Infectious Diseases, Department of Medicine, University of Pennsylvania
name: Ebbing Lautenbach, MD, MPH, MSCE
role: PRINCIPAL_INVESTIGATOR
References: