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Status unknownNCT02472600R-GNOSIS WP3Updated Dec 7, 2017

Eradication of Antibiotic-resistant Bacteria Through Antibiotics and Fecal Bacteriotherapy

A Phase 2 interventional study of Colistin and Neomycin in Intestinal Colonization With Multidrug-resistant Bacteria, sponsored by Stephen Harbarth. Status unknown at 4 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-12-07.

Sponsored by Stephen Harbarth · Phase 2, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Dec 2017), so the status shown — last known as Active, not recruiting — may be out of date.
Phase
Phase 2
Study type
Interventional
Enrollment
39
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This investigator initiated,international, multicenter open-label, randomized controlled trial aims to assess whether a 5 day course of oral nonabsorbable antibiotics (colistin sulfate 2 million IU per os 4x/day and neomycin sulfate 500 mg (salt) per os 4x/day ) followed by fecal microbiota transplantation (administered either via nasogastric administration or via capsules) is effective at eradicating intestinal carriage of beta-lactamase producing Enterobacteriaceae (ESBL-E) and carbapenemase producing Enterobacteriaceae (CPE). compared to no intervention (current standard of care) in adult non-immunosuppressed patients .

Read the detailed description

In recent years a certain family of bacteria (Enterobacteriaceae) that colonizes the human gastrointestinal tract but can also cause severe infections has increasingly become resistant to antibiotics by acquiring enzymes that can inactivate a wide array of these valuable drugs. Depending on the class of beta-lactam antibiotics that these enzymes can inactivate, these bacteria are either designated as extended spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) or carbapenemase producing Enterobacteriaceae (CPE).

The R-GNOSIS project which is financed by the European Commission combines five separate international clinical studies (work packages 2 to 6) that examine intervention strategies to reduce carriage, infection and spread of these bacteria. This study (work package 3 of R-GNOSIS) will be conducted in 4 centers in 3 European countries (Switzerland, France, The Netherlands) and Israel. The study will examine whether it is possible to eradicate intestinal carriage with ESBL-E and CPE by administering a 5 day course of oral nonabsorbable antibiotics (colistin sulfate and neomycin sulfate) followed by administration of "healthy" stool flora obtained from a healthy volunteer donor ("fecal microbiota transplantation" or FMT). The "healthy" stool flora for this procedure will be obtained from carefully selected healthy volunteers that have been tested for a wide variety of infectious diseases and do not show any risk factors or risky behavior for transmittable diseases. Once the fecal material has been processed it will be frozen at -80°C for up to six months until administration to patients (via capsules or via a nasogastric tube). FMT has been successfully used to treat recurrent infections with a specific pathogen (Clostridium difficile) and has proven safe and effective for this indication but has never been studied with the aim of eradicating multidrug-resistant organisms.

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Conditions studied

  • Intestinal Colonization With Multidrug-resistant Bacteria

Keywords

  • extended spectrum beta-lactamase producing enterobacteriaceae
  • carbapenemase producing enterobacteriaceae
  • multidrug resistant bacteria
03

In context

Lead sponsor

This is the only study on the registry with Stephen Harbarth as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Adult patients (>= 18 years at date of inclusion)
  • Ability to provide informed consent
  • Documented intestinal carriage of ESBL-E and / or CPE by stool culture at baseline (visit 0)
  • IF COLONIZED WITH ESBL-E ONLY (WITHOUT CPE): At least one episode of symptomatic infection with ESBL-E requiring systemic antibiotic therapy within the last 180 days before date of inclusion (based on the last day of antibiotic therapy for that infection)

Exclusion criteria

Exclusion Criteria:

  • Pregnancy or planned pregnancy
  • Breastfeeding
  • Difficult / impossible follow-up
  • Allergy or other contraindication to one of the study drugs
  • Recurrent aspirations / chronic dysphagia
  • Resistance to colistin (defined as MIC> 2 mg/l) of any of the ESBL-E or CPE strains isolated at baseline
  • Estimated life expectancy \< 6 months
  • Treatment with any systemic antibiotic on the day of inclusion

  • Severe immunodeficiency

    • Systemic chemotherapy ≤30 days from baseline or planned chemotherapy within the next 6 months
    • Human Immunodeficiency Virus (HIV) with CD4 count \< 250/mcl
    • Prolonged use of steroids (prednisone equivalent ≥ 60 mg per day for >= 30 days) or other immunosuppressive medications
    • neutropenia with absolute neutrophil count \<1000/μL,
    • Solid organ transplant
    • Hematopoeitic stem cell transplant recipients
    • Other causes of severe immunodeficiency
  • Current hospitalization in an Intensive Care Unit
  • Estimated glomerular filtration rate (CKD-EPI) \< 15 ml/min/1.73m2
  • Severe food allergy (anaphylaxis, urticaria)
  • Unavailability of compatible FMT preparation (with regard to donor / recipient cytomegalovirus, Epstein-Barr virus and toxoplasma serology)
  • Anatomic contraindication to the placement of a nasogastric tube (only if FMT application via nasogastric tube)
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Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
39 participants (actual)

Study arms

  • Active comparator
    colistin + neomycin followed by FMT

    CAPSULE APPROACH: Treatment days 1-5 * Colistin sulphate 2 million IU per os 4x/day (for 5 days) * Neomycin sulphate 500 mg (salt) per os 4x/day (for 5 days) Treatment day 6: no treatment Treatment days 7 and 8: -15 capsules of capsulized Fecal microbiota transplantation (FMT) per os per day NASOGASTRIC TUBE APPROACH: Treatment days 1-5 * Colistin sulphate 2 million IU per os 4x/day (for 5 days) * Neomycin sulphate 500 mg (salt) per os 4x/day (for 5 days) Treatment day 6 and 7: - Omeprazole 20 mg per os 1 dose on the evening of day 6 and on the morning of day 7 Treatment day 7: - Infusion of 80 ml of a standardized stool suspension through a nasogastric tube - Fecal microbiota transplantation (FMT)

    Drug: Colistin · Drug: Neomycin · Drug: Fecal microbiota transplantation (FMT) · Drug: Omeprazole

  • No intervention
    No intervention

    Control arm without any intervention

Interventions

  • DrugColistin

    Also known as: Polymyxin E, Diarönt® mono, A07AA10

  • DrugNeomycin

    Also known as: Neomycin Sulfate X-Gen, A01AB08

  • DrugFecal microbiota transplantation (FMT)

    FMT consist in the administration of fecal material obtained from healthy donors that has been diluted, homogenized, filtered and reconcentrated. In this study the processed fecal material will be frozen at -80°C after processing and will be administered to patients for up to six months after freezing via a nasogastric tube or via capsules.

    Also known as: Fecal bacteriotherapy, Feces transplantation

  • DrugOmeprazole

    Administered to inhibit gastric acid secretion before FMT administration if FMT administered via nasogastric tube approach (not used for capsule approach).

    Also known as: A02BC01

06

What researchers measure

Primary outcomes

  1. Intestinal carriage of ESBL-E / CRE

    Intestinal carriage of ESBL-E / CRE (absence / presence by stool culture of any ESBL-E and / or CRE with enrichment independent of type of carriage at baseline) 35 to 48 days after randomization

    Time frame: 35 to 48 days after randomization

Secondary outcomes

  1. Intestinal carriage of ESBL-E / CRE

    Intestinal ESBL-E or CRE carriage (detected / not detected) by stool culture during the other follow-up visits

    Time frame: 6 months after randomization

  2. Occurrence of any adverse drug reaction

    Time frame: 6 months

  3. Occurrence of any adverse event

    Time frame: 6 months

  4. Occurrence of any serious adverse event

    Time frame: 6 months

  5. Occurrence of any gastrointestinal adverse event

    Time frame: 6 months

  6. Isolation of any not intrinsically colistin resistant strain of Enterobacteriaceae during follow-up (MIC> 2mg/l)

    Time frame: 6 months

  7. Comparison between treatment groups of the change (relative to baseline) in the proportion of bacterial taxa and antibiotic resistance genes over time

    Time frame: 6 months

  8. Comparison of the global microbiota composition and diversity between the groups with FMT from the same donor and the groups with FMT from different donors

    Time frame: 6 months

  9. Assess the stability of the microbiome of donor stools after 3 months of frozen storage

    Aliquots from a random sample of donations will also be taken for metagenomic analysis performed after 3 months of storage at -80°C to assess the long-term impact of freezing on the microbiome

    Time frame: 3 months of freezing (donor stools)

  10. Assess the stability of the microbiome of donor stools after 6 months of frozen storage

    Aliquots from a random sample of donations will also be taken for metagenomic analysis performed after 6 months of storage at -80°C to assess the long-term impact of freezing on the microbiome

    Time frame: 6 months of freezing (donor stools)

  11. Assess the stability of the microbiome of donor stools after 12 months of frozen storage

    Aliquots from a random sample of donations will also be taken for metagenomic analysis performed after 12 months of storage at -80°C to assess the long-term impact of freezing on the microbiome

    Time frame: 12 months of freezing (donor stools)

  12. Assess the stability of the microbiome of donor stools after 18 months of frozen storage

    Aliquots from a random sample of donations will also be taken for metagenomic analysis performed after 18 months of storage at -80°C to assess the long-term impact of freezing on the microbiome

    Time frame: 18 months of freezing (donor stools)

  13. Assess the stability of the microbiome of donor stools after 24months of frozen storage

    Aliquots from a random sample of donations will also be taken for metagenomic analysis performed after 24 months of storage at -80°C to assess the long-term impact of freezing on the microbiome

    Time frame: 24 months of freezing (donor stools)

  14. ESBL-E and CRE infections per 100 patient months at risk (first infection with either)

    Time frame: 6 months

  15. Use of any antibiotics active against all of the colonizing ESBL-E / CRE strains

    Time frame: 6 months

  16. Use of any antibiotics active against at least one of the colonizing ESBL-E / CRE strains

    Time frame: 6 months

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Study locations

4 sites
  • Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon
    Clichy, 92110, France
  • Sourasky Medical Center
    Tel Aviv, Israel
  • Universitair Medisch Centrum Utrecht,
    Utrecht, Netherlands
  • Geneva University Hospitals
    Geneva, Switzerland
08

References and documents

Publications

  • Huttner B, Haustein T, Uckay I, Renzi G, Stewardson A, Schaerrer D, Agostinho A, Andremont A, Schrenzel J, Pittet D, Harbarth S. Decolonization of intestinal carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae with oral colistin and neomycin: a randomized, double-blind, placebo-controlled trial. J Antimicrob Chemother. 2013 Oct;68(10):2375-82. doi: 10.1093/jac/dkt174. Epub 2013 May 29. PubMed 23719234 ↗
  • Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA. 2014 Nov 5;312(17):1772-8. doi: 10.1001/jama.2014.13875. Erratum In: JAMA. 2015 Feb 17;313(7):729. PubMed 25322359 ↗
  • de Lastours V, Poirel L, Huttner B, Harbarth S, Denamur E, Nordmann P. Emergence of colistin-resistant Gram-negative Enterobacterales in the gut of patients receiving oral colistin and neomycin decontamination. J Infect. 2020 May;80(5):578-606. doi: 10.1016/j.jinf.2020.01.003. Epub 2020 Jan 15. No abstract available. PubMed 31954100 ↗
  • Huttner BD, de Lastours V, Wassenberg M, Maharshak N, Mauris A, Galperine T, Zanichelli V, Kapel N, Bellanger A, Olearo F, Duval X, Armand-Lefevre L, Carmeli Y, Bonten M, Fantin B, Harbarth S; R-Gnosis WP3 study group. A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial. Clin Microbiol Infect. 2019 Jul;25(7):830-838. doi: 10.1016/j.cmi.2018.12.009. Epub 2019 Jan 4. PubMed 30616014 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 7, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT02472600
Lead sponsor
Stephen Harbarth
Collaborators
European Commission
Responsible party
Stephen Harbarth (Professor, University Hospital, Geneva) — Sponsor-investigator
First posted
Jun 16, 2015
Start date
Feb 2016
Primary completion
Nov 29, 2017
Completion
Mar 2018 (estimated)
Last update
Dec 7, 2017

Study contacts

Stephan J Harbarth, MD, MS
principal investigator · Geneva University Hospitals and University of Geneva

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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This study is status unknown, as verified in Dec 2017. You cannot join it, but the record below documents what was studied.

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