Severe Clostridium Difficile InfectionPhase 2NCT03970200

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

A Phase 2 study testing Penn Microbiome Therapy - 001, Penn Microbiome Therapy - 002 and Penn Microbiome Therapy - 003 in people with Severe Clostridium Difficile Infection and Severe-Complicated/Fulminant Clostridium Difficile Infection, run by University of Pennsylvania at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Severe Clostridium Difficile Infection, Severe-Complicated/Fulminant Clostridium Difficile Infection
What is being tested?: Penn Microbiome Therapy - 001, Penn Microbiome Therapy - 002 and Penn Microbiome Therapy - 003
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 15 participants
Where: 1 siteUnited States
Study dates: 16 Jan 2020to 14 May 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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:

Show all 23Show fewer

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Hospital of the Univeristy of Pennsylvania
Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

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

Conditions: Severe Clostridium Difficile Infection, Severe-Complicated/Fulminant Clostridium Difficile Infection
Being tested: Penn Microbiome Therapy - 001, Penn Microbiome Therapy - 002, Penn Microbiome Therapy - 003, Antibiotics
Medical subject headings: Clostridium Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Penn Microbiome Therapy - 001Drug
Also called PMT-001
Fecal Microbiota for Transplant, enema product
Penn Microbiome Therapy - 002Drug
Also called PMT-002
Fecal Microbiota for Transplant, suspension product
Penn Microbiome Therapy - 003Drug
Also called PMT-003
Fecal Microbiota for Transplant, capsule product
AntibioticsDrug
Standard of care antibiotics

Study groups in NCT03970200
Study group	Role	What they receive
No investigational product	Active comparator	Participants who receive the antibiotics usually prescribed for C diff infection. Receives: Drug: Antibiotics
Upper gastrointestinal Fecal Microbiota Transplantation	Experimental	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 Receives: Drug: Penn Microbiome Therapy - 002; Drug: Penn Microbiome Therapy - 003; Drug: Antibiotics
Lower gastrointestinal Fecal Microbiota Transplantation	Experimental	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). Receives: Drug: Penn Microbiome Therapy - 001; Drug: Antibiotics

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 3 Days

Secondary outcomes (7)

All-cause Mortality at 30 Days Following Last Fecal Microbiota Transplantation (FMT)
Number of deaths within 30 days of the last FMT
Measured: 30 Days
All-cause Mortality at 60-days Following Last FMT
Number of deaths within 60 days of the last FMT
Measured: 60 Days
Colectomy or Diverting Ileostomy Within 30 Days After Last FMT
Measured: 30 Days
Cumulative Days of Hospitalization From Enrollment Until 30 Days After FMT
Measured: 30 Days
Cumulative Days in Intensive Care Unit From Enrollment Until 30 Days After Last FMT
Measured: 30 Days
Bacteremia From Enrollment Until 30 Days After Last FMT
Measured: 30 Days
Repeat Hospital Admission Within 60 Days of Discharge From Index Hospitalization
Measured: 60 Days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Jan 202014 May 2022

First posted31 May 2019
Study start16 Jan 2020
Primary completion21 Nov 2021
Study completion14 May 2022

Why it stopped: Administrative reasons.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Severe Clostridium Difficile InfectionStudies of the same condition, open and under way.
More trials run by University of PennsylvaniaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Randomized, open label, comparative
Masking: None (open label)
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03970200
Sponsor's protocol ID: IRB # 832962
Status last verified: Oct 2023
First submitted: 17 Apr 2019
Last updated: 30 Oct 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 30 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03970200
Acronym / sponsor ID: IRB # 832962
Conditions: Severe Clostridium Difficile Infection, Severe-Complicated/Fulminant Clostridium Difficile Infection
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Administrative reasons.
Enrolment: 15 participants (actual)
Lead sponsor: University of PennsylvaniaUniversity, hospital or other
Study start: 16 Jan 2020 (actual)
Primary completion: 21 Nov 2021 (actual)
Study completion: 14 May 2022 (actual)
First posted: 31 May 2019 (actual)
Results: Posted 30 Oct 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3
Model description: Randomized, open label, comparative

Arm	Type	Receives
No investigational product	Active comparator	Drug: AntibioticsParticipants who receive the antibiotics usually prescribed for C diff infection.
Upper gastrointestinal Fecal Microbiota Transplantation	Experimental	Drug: Penn Microbiome Therapy - 002, Drug: Penn Microbiome Therapy - 003, Drug: AntibioticsParticipants 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
Lower gastrointestinal Fecal Microbiota Transplantation	Experimental	Drug: Penn Microbiome Therapy - 001, Drug: AntibioticsParticipants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given through the rectum by an enema (lower delivery).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (23 listed)

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.

Key exclusion criteria (8 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Penn Microbiome Therapy - 001Also: PMT-001Fecal Microbiota for Transplant, enema product	Drug	Lower gastrointestinal Fecal Microbiota Transplantation
Penn Microbiome Therapy - 002Also: PMT-002Fecal Microbiota for Transplant, suspension product	Drug	Upper gastrointestinal Fecal Microbiota Transplantation
Penn Microbiome Therapy - 003Also: PMT-003Fecal Microbiota for Transplant, capsule product	Drug	Upper gastrointestinal Fecal Microbiota Transplantation
AntibioticsStandard of care antibiotics	Drug	Lower gastrointestinal Fecal Microbiota Transplantation, No investigational product, Upper gastrointestinal Fecal Microbiota Transplantation

Primary outcome

Number of Subjects With Resolution of Symptoms After Treatment With One of the PMT Suite of Products.
Time frame: 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

7 secondary outcomes

All-cause Mortality at 30 Days Following Last Fecal Microbiota Transplantation (FMT)
Time frame: 30 Days
All-cause Mortality at 60-days Following Last FMT
Time frame: 60 Days
Colectomy or Diverting Ileostomy Within 30 Days After Last FMT
Time frame: 30 Days
Cumulative Days of Hospitalization From Enrollment Until 30 Days After FMT
Time frame: 30 Days
Cumulative Days in Intensive Care Unit From Enrollment Until 30 Days After Last FMT
Time frame: 30 Days
Bacteremia From Enrollment Until 30 Days After Last FMT
Time frame: 30 Days
Repeat Hospital Admission Within 60 Days of Discharge From Index Hospitalization
Time frame: 60 Days

Results and safety

Results posted to the registry on 30 Oct 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
No Investigational Product	5	3
Upper Gastrointestinal Fecal Microbiota Transplantation	4	2
Lower Gastrointestinal Fecal Microbiota Transplantation	6	4

Primary outcome: Number of Subjects With Resolution of Symptoms After Treatment With One of the PMT Suite of Products.

Time frame: 3 Days. Count of participants. Unit: Participants

Measure	No Investigational Product n = 5	Upper Gastrointestinal Fecal Microbiota Transplantation n = 4	Lower Gastrointestinal Fecal Microbiota Transplantation n = 6
Value	4	3	5

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: 6 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
No Investigational Product	3 of 5 (60%)	4 of 5 (80%)	2 of 5
Upper Gastrointestinal Fecal Microbiota Transplantation	3 of 4 (75%)	4 of 4 (100%)	2 of 4
Lower Gastrointestinal Fecal Microbiota Transplantation	4 of 6 (66.7%)	6 of 6 (100%)	1 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ebbing Lautenbach, MD, MPH, MSCE principal investigator

Division of Infectious Diseases, Department of Medicine, University of Pennsylvania

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With Resolution of Symptoms After Treatment With One of the PMT Suite of Products. (time frame: 3 Days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03970200.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2023.