Eradication of Antibiotic-resistant Bacteria Through Antibiotics and Fecal Bacteriotherapy

NCT02472600 | Unknown Phase 2

• 2 other identifiers: 13-2662014-003727-22
• Study Type: interventional
• Target: 39
• Locations: 4 countries
• Sites: 4

Brief 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 .

Conditions

Intestinal Colonization With Multidrug-resistant Bacteria

Keywords

extended spectrum beta-lactamase producing enterobacteriaceae; carbapenemase producing enterobacteriaceae; multidrug resistant bacteria

Outcome Measures

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

  35 to 48 days after randomization

Secondary Outcomes (16)

• Intestinal carriage of ESBL-E / CRE

  6 months after randomization

• Occurrence of any adverse drug reaction

  6 months

• Occurrence of any adverse event

  6 months

• Occurrence of any serious adverse event

  6 months

• Occurrence of any gastrointestinal adverse event

  6 months

Study Arms (2)

colistin + neomycin followed by FMT

ACTIVE COMPARATOR

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

Colistin DRUG

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

colistin + neomycin followed by FMT

Neomycin DRUG

Also known as: Neomycin Sulfate X-Gen, A01AB08

colistin + neomycin followed by FMT

Fecal microbiota transplantation (FMT) DRUG

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

colistin + neomycin followed by FMT

Omeprazole DRUG

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

colistin + neomycin followed by FMT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide informed consent
• Documented intestinal carriage of ESBL-E and / or CPE by stool culture at baseline (visit 0)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Stephen Harbarth: lead
• European Commission: collaborator

Study Sites (4)

Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon

Clichy, 92110, France

Location

Sourasky Medical Center

Tel Aviv, Israel

Location

Universitair Medisch Centrum Utrecht,

Utrecht, Netherlands

Location

Geneva University Hospitals

Geneva, Switzerland

Location

Related Publications (4)

• 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.

  PMID: 23719234 BACKGROUND

• 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.

  PMID: 25322359 BACKGROUND

• 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.

  PMID: 31954100 DERIVED

• 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.

  PMID: 30616014 DERIVED

Related Links

• Official website of the R-GNOSIS project

MeSH Terms

Interventions

Colistin; Neomycin; Fecal Microbiota Transplantation; Omeprazole

Intervention Hierarchy (Ancestors)

Polymyxins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Antimicrobial Cationic Peptides; Peptides; Amino Acids, Peptides, and Proteins; Antimicrobial Peptides; Pore Forming Cytotoxic Proteins; Membrane Proteins; Proteins; Aminoglycosides; Glycosides; Carbohydrates; Biological Therapy; Therapeutics; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Stephan J Harbarth, MD, MS

  Geneva University Hospitals and University of Geneva

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 4, 2015
• First Posted: June 16, 2015
• Study Start: February 1, 2016
• Primary Completion: November 29, 2017
• Study Completion: March 1, 2018
• Last Updated: December 7, 2017

Record last verified: 2017-12

Locations

FR (1); IL (1); NL (1); CH (1)