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PMT for Severe-CDI

Primary Purpose

Severe Clostridium Difficile Infection, Severe-Complicated/Fulminant Clostridium Difficile Infection

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Penn Microbiome Therapy - 001
Penn Microbiome Therapy - 002
Penn Microbiome Therapy - 003
Antibiotics
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Clostridium Difficile Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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/F-CDI per current 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. 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. 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 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

Sites / Locations

  • Hospital of the Univeristy of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

No investigational product

Upper gastrointestinal Fecal Microbiota Transplantation

Lower gastrointestinal Fecal Microbiota Transplantation

Arm Description

Participants who receive the antibiotics usually prescribed for C diff infection.

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

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).

Outcomes

Primary Outcome Measures

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 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 Outcome Measures

Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE V5.0
All-cause mortality at 30- and 60-days following last FMT Colectomy or diverting ileostomy within 30 days after last FMT Cumulative days of hospitalization from enrollment until 30 days after FMT Cumulative days in intensive care unit from enrollment until 30 days after last FMT Bacteremia from enrollment until 30 days after last FMT Repeat hospital admission within 60 days of discharge from index hospitalization
Frequency solicited adverse events (AEs) as assessed by CTCAE V5.0
Frequency serious adverse events (SAEs) as assessed by CTCAE V5.0
Frequency of AEs of special interest (AESIs) as assessed by CTCAE V5.0

Full Information

First Posted
April 17, 2019
Last Updated
January 25, 2023
Sponsor
University of Pennsylvania
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1. Study Identification

Unique Protocol Identification Number
NCT03970200
Brief Title
PMT for Severe-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

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Terminated
Why Stopped
Administrative reasons.
Study Start Date
January 16, 2020 (Actual)
Primary Completion Date
November 21, 2021 (Actual)
Study Completion Date
May 14, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Clostridium Difficile Infection, Severe-Complicated/Fulminant Clostridium Difficile Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized, open label, comparative
Masking
None (Open Label)
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
No investigational product
Arm Type
Active Comparator
Arm Description
Participants who receive the antibiotics usually prescribed for C diff infection.
Arm Title
Upper gastrointestinal Fecal Microbiota Transplantation
Arm Type
Experimental
Arm Description
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
Arm Title
Lower gastrointestinal Fecal Microbiota Transplantation
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Penn Microbiome Therapy - 001
Other Intervention Name(s)
PMT-001
Intervention Description
Fecal Microbiota for Transplant, enema product
Intervention Type
Drug
Intervention Name(s)
Penn Microbiome Therapy - 002
Other Intervention Name(s)
PMT-002
Intervention Description
Fecal Microbiota for Transplant, suspension product
Intervention Type
Drug
Intervention Name(s)
Penn Microbiome Therapy - 003
Other Intervention Name(s)
PMT-003
Intervention Description
Fecal Microbiota for Transplant, capsule product
Intervention Type
Drug
Intervention Name(s)
Antibiotics
Intervention Description
Standard of care antibiotics
Primary Outcome Measure Information:
Title
Number of subjects with resolution of symptoms after treatment with one of the PMT suite of products.
Description
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 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
7 Days
Secondary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE V5.0
Description
All-cause mortality at 30- and 60-days following last FMT Colectomy or diverting ileostomy within 30 days after last FMT Cumulative days of hospitalization from enrollment until 30 days after FMT Cumulative days in intensive care unit from enrollment until 30 days after last FMT Bacteremia from enrollment until 30 days after last FMT Repeat hospital admission within 60 days of discharge from index hospitalization
Time Frame
180 Days
Title
Frequency solicited adverse events (AEs) as assessed by CTCAE V5.0
Time Frame
180 Days
Title
Frequency serious adverse events (SAEs) as assessed by CTCAE V5.0
Time Frame
180 Days
Title
Frequency of AEs of special interest (AESIs) as assessed by CTCAE V5.0
Time Frame
180 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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/F-CDI per current 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. 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. 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ebbing Lautenbach, MD, MPH, MSCE
Organizational Affiliation
Division of Infectious Diseases, Department of Medicine, University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital of the Univeristy of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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PMT for Severe-CDI

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