Intestinal Colonization With Multidrug-resistant Bacteria Clinical Trial
— R-GNOSIS WP3Official title:
A Randomized Controlled Multicenter Trial of a Five Day Course of Oral Colistin and Neomycin Followed by Restoration of the Gut Microbiota Using Fecal Transplantation to Eradicate Intestinal Carriage of Extended Spectrum Beta-lactamase or Carbapenemase-producing Enterobacteriaceae in High-risk Patients
| Verified date | December 2017 |
| Source | University Hospital, Geneva |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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 .
| Status | Active, not recruiting |
| Enrollment | 39 |
| Est. completion date | March 2018 |
| Est. primary completion date | November 29, 2017 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
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: - 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) |
| Country | Name | City | State |
|---|---|---|---|
| France | Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon | Clichy | |
| Israel | Sourasky Medical Center | Tel Aviv | |
| Netherlands | Universitair Medisch Centrum Utrecht, | Utrecht | |
| Switzerland | Geneva University Hospitals | Geneva |
| Lead Sponsor | Collaborator |
|---|---|
| Stephen Harbarth | European Commission |
France, Israel, Netherlands, Switzerland,
Huttner B, Haustein T, Uçkay I, Renzi G, Stewardson A, Schaerrer D, Agostinho A, Andremont A, Schrenzel J, Pittet D, Harbarth S. Decolonization of intestinal carriage of extended-spectrum ß-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. — View Citation
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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | Intestinal carriage of ESBL-E / CRE | Intestinal ESBL-E or CRE carriage (detected / not detected) by stool culture during the other follow-up visits | 6 months after randomization | |
| Secondary | Occurrence of any adverse drug reaction | 6 months | ||
| Secondary | Occurrence of any adverse event | 6 months | ||
| Secondary | Occurrence of any serious adverse event | 6 months | ||
| Secondary | Occurrence of any gastrointestinal adverse event | 6 months | ||
| Secondary | Isolation of any not intrinsically colistin resistant strain of Enterobacteriaceae during follow-up (MIC> 2mg/l) | 6 months | ||
| Secondary | Comparison between treatment groups of the change (relative to baseline) in the proportion of bacterial taxa and antibiotic resistance genes over time | 6 months | ||
| Secondary | 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 | 6 months | ||
| Secondary | 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 | 3 months of freezing (donor stools) | |
| Secondary | 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 | 6 months of freezing (donor stools) | |
| Secondary | 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 | 12 months of freezing (donor stools) | |
| Secondary | 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 | 18 months of freezing (donor stools) | |
| Secondary | 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 | 24 months of freezing (donor stools) | |
| Secondary | ESBL-E and CRE infections per 100 patient months at risk (first infection with either) | 6 months | ||
| Secondary | Use of any antibiotics active against all of the colonizing ESBL-E / CRE strains | 6 months | ||
| Secondary | Use of any antibiotics active against at least one of the colonizing ESBL-E / CRE strains | 6 months |