Eradication of Antibiotic-resistant Bacteria Through Antibiotics and Fecal Bacteriotherapy
NCT ID: NCT02472600
Last Updated: 2017-12-07
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE2
39 participants
INTERVENTIONAL
2016-02-29
2018-03-31
Brief Summary
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Detailed Description
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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.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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)
Colistin
Neomycin
Fecal 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.
Omeprazole
Administered to inhibit gastric acid secretion before FMT administration if FMT administered via nasogastric tube approach (not used for capsule approach).
No intervention
Control arm without any intervention
No interventions assigned to this group
Interventions
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Colistin
Neomycin
Fecal 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.
Omeprazole
Administered to inhibit gastric acid secretion before FMT administration if FMT administered via nasogastric tube approach (not used for capsule approach).
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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)
18 Years
ALL
No
Sponsors
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European Commission
OTHER
Stephen Harbarth
OTHER
Responsible Party
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Stephen Harbarth
Professor
Principal Investigators
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Stephan J Harbarth, MD, MS
Role: PRINCIPAL_INVESTIGATOR
Geneva University Hospitals and University of Geneva
Locations
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Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon
Clichy, , France
Sourasky Medical Center
Tel Aviv, , Israel
Universitair Medisch Centrum Utrecht,
Utrecht, , Netherlands
Geneva University Hospitals
Geneva, , Switzerland
Countries
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References
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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.
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.
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.
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.
Related Links
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Official website of the R-GNOSIS project
Other Identifiers
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2014-003727-22
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
13-266
Identifier Type: -
Identifier Source: org_study_id