Carbapenem-Resistant Enterobacteriaceae InfectionPhase 2/3NCT04146337
Fecal Microbiota Transplantation for Carbapenem-resistant Enterobacteriaceae
A Phase 2/3 study testing FMT in people with Carbapenem-Resistant Enterobacteriaceae Infection, run by Rambam Health Care Campus at 1 site in Israel.
Trial summary
2:1, open-label, single center, randomized controlled trial comparing FMT vs. no intervention for CRE carriers, Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Carbapenem-Resistant Enterobacteriaceae Infection
- What is being tested?
- FMT
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteIsrael
- Study dates
- 12 Oct 2020to 30 Jun 2022
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
We will include adult inpatients ≥18 years positive for CRE of any strain and resistance mechanism in rectal surveillance stool samples, with or without CRE clinical samples. We will mandate a positive rectal swab within one week before randomization. Several exclusion criteria may change throughout the patients' hospitalization and we will follow-up patients for these criteria until reaching eligibility or not (designed as (for follow-up)). Non-eligible patients discharged will be re-evaluated for inclusion when re-admitted.
We will exclude:
- Pregnant women
- Patients with severe neutropenia (<100/µl) (for follow-up)
- Severe GVHD involving the gastrointestinal involvment (for follow-up)
- Patients with inflammatory bowel disease (Crohn's or ulcerative colitis)
- Patients with intestinal perforation or severe abdominal infection (for follow-up)
- Patients carrying a colostomy, ileostomy or similar
- Inability or contra-indication to take oral medications (intestinal obstruction, suspected perforation, peritonitis) (for follow-up)
- Severe food allergies
- Severe diarrhea (for follow-up)
- Inability to provide informed consent (for follow-up)
- Refusal of primary care physician
- Patients treated with antibiotics within the 2 days before fulfilling all other eligibility criteria (for follow-up)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Fecal Microbiota Transplantation for Eradication of Carbapenem-resistant Enterobacteriaceae Colonization: Randomized Control Trial
2:1, open-label, single center, randomized controlled trial comparing FMT vs. no intervention for CRE carriers,
Read the detailed description
Antibiotic resistance has emerged worldwide and is of major concern leading to multidrug resistant (MDR) bacteria that are widely spread and are a major factor in morbidity and mortality in health-care settings. Among MDRs, carbapenem resistant Enterobacteriaceae (CRE) are of special concern, receiving the highest classification of "urgent threat level" in the US President Report. Consistent mortality rates of 40-50% are observed among inpatients with infections caused by CRE in hospitals worldwide, related mainly to unavailable, delayed or ineffective antibiotic treatment options. The extremely high mortality rates of patients with CRE infections have driven efforts to prevent the acquisition and spread of these bacteria in hospitals. These include screening for carriage, contact isolation of carriers, cohorting, dedicated healthcare staff and other infection control measures. These strategies have been proven as effective but are cumbersome and expensive. In most locations these strategies failed to completely eradicate CRE endemicity. CRE decolonization (eradication of colonization) might offer a double benefit: reducing the risk for the individual carrier to develop an infection due to the resistant strain (by that, potentially lowering the mortality risk) and preventing the bacteria from spreading to other patients, exposing them to the same hazard. Fecal microbiota transplantation (FMT), in which fecal material enriched with commensal microorganisms is transferred from a healthy donor, have proven efficacy in the treatment of recurrent Clostridium difficile infection (CDI) in multiple trails. Major adverse events that has been reported so far are mostly related to the route of administration (aspiration during nasogastric tube administration/colonoscopy). Other adverse events include mostly GI related symptoms (diarrhea, nausea, belching) and are self limited and resolve in few hours. FMT seems to be safe and effective both in immunocompetent and immunocompromised patients. The high efficacy of FMT in the treatment of a multi-drug resistant pathogen such as Clostridium difficile, suggest that it might be an efficient tool for other MDR pathogens (e.g. CRE). The potential of FMT to restore the gut microbiome and compete with residual resistant strains offer a novel way to fight the current MDR epidemic.
The investigators aim to assess the effects of FMT on colonization and clinical infections with CRE. The investigators will apply FMT on a cohort of CRE carriers in a single center in Israel. FMT will be given by capsules for 2 consecutive days followed by rectal sampling at predefined time-point in the following 6 months.
- Being tested
- FMT
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FMTBiological
Fecal microbiota in frozen capsules
| Study group | Role | What they receive |
|---|---|---|
| Fecal microbiota transplantation (FMT) | Experimental | FMT regimen: Patients will be given capsulized FMT 15 capsules a day for two consecutive days after a fast of 8 hours before FMT. Stool will be collected before and after the intervention for genomic analysis of CRE strains, analysis of microbiome and metabolome. Receives: Biological: FMT |
| Control | No intervention | Routine follow-up |
What is being measured
The primary outcome is the main question the study is designed to answer.
CRE eradication
Number of participants achieving CRE eradication at 28 days, defined as 3 consecutive negative rectal cultures, with polymerase chain reaction preformed in the last sample. For patients with clinical infections, eradication definition will include a negative culture from the site of infection, if relevant at the time of eradication.
Measured: 28 days
Secondary outcomes (6)
CRE eradication rates at day 7, day 14, and 3 & 6 months
Number of participants achieving CRE eradication rates at day 7, day 14, and 3 \& 6 months
Measured: days 7, 14, months 3, 6
Mortality
Number of participants who died by 28-day and 6 month
Measured: 28-day and 6 months
Bacteremia
Number of participants with CRE bacteremia and any bacteremia
Measured: 6 months
CRE infection
Number of participants with non-bacteremic new clinically-significant CRE infections
Measured: 6 months
Hospitalization days
Totals days in-hospital
Measured: 6 months
Adverse events
Number of participants with: pneumonia within a week after the intervention; dyspeptic complaints collected at the time of rectal sampling; changes in bowel habit including diarrhea and constipation; discontinuation of FMT before completing the study protocol
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2019
- Study start12 Oct 2020
- Primary completion31 Dec 2021
- Study completion30 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carbapenem-Resistant Enterobacteriaceae InfectionStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rambam Health Care Campus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Haggay Bar Yoseph, MD, Principal investigator, Rambam Health Care Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04146337
- Sponsor's protocol ID
- 0338-19
- Status last verified
- Nov 2022
- First submitted
- 29 Oct 2019
- Last updated
- 29 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Share by contact with authors
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fecal Microbiota Transplantation for Eradication of Carbapenem-resistant Enterobacteriaceae Colonization: Randomized Control Trial
- ClinicalTrials.gov ID
- NCT04146337
- Acronym / sponsor ID
- 0338-19
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Rambam Health Care CampusUniversity, hospital or other
- Study start
- 12 Oct 2020 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 30 Jun 2022 (actual)
- First posted
- 31 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
2:1, open-label, single center, randomized controlled trial comparing FMT vs. no intervention for CRE carriers,
Detailed description
Antibiotic resistance has emerged worldwide and is of major concern leading to multidrug resistant (MDR) bacteria that are widely spread and are a major factor in morbidity and mortality in health-care settings. Among MDRs, carbapenem resistant Enterobacteriaceae (CRE) are of special concern, receiving the highest classification of "urgent threat level" in the US President Report. Consistent mortality rates of 40-50% are observed among inpatients with infections caused by CRE in hospitals worldwide, related mainly to unavailable, delayed or ineffective antibiotic treatment options. The extremely high mortality rates of patients with CRE infections have driven efforts to prevent the acquisition and spread of these bacteria in hospitals. These include screening for carriage, contact isolation of carriers, cohorting, dedicated healthcare staff and other infection control measures. These strategies have been proven as effective but are cumbersome and expensive. In most locations these strategies failed to completely eradicate CRE endemicity. CRE decolonization (eradication of colonization) might offer a double benefit: reducing the risk for the individual carrier to develop an infection due to the resistant strain (by that, potentially lowering the mortality risk) and preventing the bacteria from spreading to other patients, exposing them to the same hazard. Fecal microbiota transplantation (FMT), in which fecal material enriched with commensal microorganisms is transferred from a healthy donor, have proven efficacy in the treatment of recurrent Clostridium difficile infection (CDI) in multiple trails. Major adverse events that has been reported so far are mostly related to the route of administration (aspiration during nasogastric tube administration/colonoscopy). Other adverse events include mostly GI related symptoms (diarrhea, nausea, belching) and are self limited and resolve in few hours. FMT seems to be safe and effective both in immunocompetent and immunocompromised patients. The high efficacy of FMT in the treatment of a multi-drug resistant pathogen such as Clostridium difficile, suggest that it might be an efficient tool for other MDR pathogens (e.g. CRE). The potential of FMT to restore the gut microbiome and compete with residual resistant strains offer a novel way to fight the current MDR epidemic.
The investigators aim to assess the effects of FMT on colonization and clinical infections with CRE. The investigators will apply FMT on a cohort of CRE carriers in a single center in Israel. FMT will be given by capsules for 2 consecutive days followed by rectal sampling at predefined time-point in the following 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fecal microbiota transplantation (FMT) | Experimental | Biological: FMTFMT regimen: Patients will be given capsulized FMT 15 capsules a day for two consecutive days after a fast of 8 hours before FMT. Stool will be collected before and after the intervention for genomic analysis of CRE strains, analysis of microbiome and metabolome. |
| Control | No intervention | –Routine follow-up |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| FMTFecal microbiota in frozen capsules | Biological | Fecal microbiota transplantation (FMT) |
Primary outcome
CRE eradication
Time frame: 28 days
Number of participants achieving CRE eradication at 28 days, defined as 3 consecutive negative rectal cultures, with polymerase chain reaction preformed in the last sample. For patients with clinical infections, eradication definition will include a negative culture from the site of infection, if relevant at the time of eradication.
6 secondary outcomes
CRE eradication rates at day 7, day 14, and 3 & 6 months
Time frame: days 7, 14, months 3, 6
Mortality
Time frame: 28-day and 6 months
Bacteremia
Time frame: 6 months
CRE infection
Time frame: 6 months
Hospitalization days
Time frame: 6 months
Adverse events
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2022.
- Individual participant dataSharing planned: Yes. Share by contact with authors
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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.
Haggay Bar Yoseph, MD principal investigator
Rambam Health Care Campus
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing FMT in people with Carbapenem-Resistant Enterobacteriaceae Infection, run by Rambam Health Care Campus at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: finished, as of the sponsor's last update on 29 Nov 2022. 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 Israel. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
CRE eradication (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Nov 2022.