Clinical trial NCT06156956: Fecal Microbiota Transplantation (FMT) to Decolonize Antibiotic - Resistant Bacteria (ARB) - New Protocol
Official title: Fecal Microbiota Transplantation to Eradicate Antibiotic-resistance Bacteria From the Gastrointestinal Tract of Patients at High Risk of Infection and/or to Cut Off the Spread of Bacteria With Dangerous Mechanisms of Antibiotic Resistance
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Drug Resistance, Bacterial
Antimicrobial Drug Resistance
Keywords: Antibiotic-resistant bacteria decolonization
Gastrointestinal tract colonization
Eradication procedure
Fecal Microbiota Transplantation
Lead sponsor: Human Biome Institute S.A.
Sponsor class: INDUSTRY
First posted: 2023-12-05
Enrollment: 200
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single group, open label, observational study with intervention (Fecal Microbiota Transplantation)
Primary purpose: TREATMENT

Brief summary: The aim of the study is to assess the safety and efficacy of new protocol fecal microbiota transplantation (FMT) in the eradication of antibiotic resistant bacteria, including those featuring of resistance to new generation antibiotics.

This study should answer the following research questions:

1. Will new treatment protocol and fully anaerobic FMT be effective in decolonization of ARB?
2. Will FMT improve the prognosis and quality of life in patients at high risk of ARB infection?

Detailed description: Fecal microbiota transplantation (FMT) was shown to be very efficient in treatment of relapsed and refractory Clostridium difficile infection and became a standard treatment. The investigators company produces and uses FMT not only in case of Clostridioides difficile colitis, but also in case of gut colonization with antibiotic-resistant bacteria and other indications as a clinical studies under Bioethical Committee approval. Company's flagship program to decolonize ARB is based on assumption that physiological gut flora may outcompete the pathogenic bacteria similarly as in case of Clostridium difficile and lead to loss of colonization.

Patients colonized with ARB are characterized by poor diversity of gut microbiome (dysbiosis), which makes them vulnerable to further infections. In case of gut mucosa injury and severe immune suppression, these colonizing bacteria may cause severe systemic infections.

During this interventional prospective, single arm, observational study, the investigators collect the information about the safety and effectiveness of FMT in gut decolonization with antibiotic-resistance bacteria (ARB) using their new treatment protocol and own full-spectrum, full-richness, full-viability anaerobic FMT.

The project protocol is based on the intervention (fecal microbiota transplantation; FMT) in capsules (or colonoscopy if per os route is not possible) applied twice - on day 7th after procedure initiation and between day 9-14 within extended period, low dose (1/6th every day) application. All patient are premedicated with non-absorbable antibiotics on days 1-5 and a bowel cleansing on day 6 from the screening. After the end of the eradication procedure, the patient proceeds to the follow-up assessment stage and is observed up to 360 days with longitudinal samples collection.

Eligibility criteria: Inclusion Criteria:

1. Age \> 6 months
2. Population of patients colonized with antibiotic-resistant bacteria, as follows:

   1. strains of antibiotic-resistant bacteria that exhibit resistance mechanisms to carbapenems (MBL+: NDM+, VIM+ or others), KPC+, OXA-48+ or confirmed resistance to carbapenems without a specific genetic mechanism
   2. strains of Enterobacteriaceae resistant to beta lactams and other antibiotics in the case of multi-drug resistance (e.g. in the ESBL resistance mechanism and others) of the types including Escherichia, Enterobacter, Klebsiella, strains of P. aeruginosa, A. baumannii (together included in, among others, the ESKAPE group)
   3. Gram (+) enterococci E. faecalis or E. faecium or other bacteria resistant to vancomycin (VRE), linezolid and strains of S. aureus resistant to methicillin (MRSA) or vancomycin
   4. other multidrug-resistant or drug-resistant strains with threatening clinical resistance mechanisms or in patients vulnerable to infection with a particular pathogen
3. Absolute neutrophil count in the peripheral blood up to 3 days before FMT \> 500/ul (in the case of tandem multiple FMTs, in patients with an expected decrease in neutrophil values, the test should be repeated before each FMT when the timeframe between FMTs is longer than 3 days, and in patients without an expected decrease in the value of neutrophils below 500 cells/ul peripheral blood counts are valid for 28 days)
4. Signing of the informed consent for participation in the study.

Exclusion Criteria:

1. Inability to obtain informed consent and lack of consent
2. Blood neutrophil count \<500/uL on the day of fecal microbiota transplantation or expected decrease to the mentioned number within 2 consecutive days
3. Active infection requiring intensive antimicrobial treatment on FMT day or the first 7 days after FMT in immunocompetent patients (without immunosuppression or immunodeficiency)
4. Clinical signs of mucositis 7 days prior to FMT
5. Contraindications to FMT via upper and lower gastrointestinal tract (e.g. perforation of the digestive tract, rectal atresia, discontinuity of the digestive tract and others)
6. Severe food allergy with the anaphylaxis history

Primary outcomes:
measure: Eradication of gut colonizing antibiotic-resistant bacteria
timeFrame: Baseline, 30, 60, 90, 180, 360 days after the end of eradication
Secondary outcomes:
measure: Increase in the diversity of the recipients' gut microbiota
timeFrame: from pre-treatment to 360 days after-treatment
Other outcomes:
measure: Infections-oriented safety profile assessment
timeFrame: During 3 months form FMT
Locations:
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, Klinika Gastroenterologii i Hepatologii
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, Klinika Pediatrii, Hematologii i Onkologii
city: Kielce
country: Poland
facility: WOJEWÓDZKI SZPITAL ZESPOLONY W KIELCACH, Klinika Chorób Zakaźnych
city: Warszawa
country: Poland
facility: WIM-PIB: Klinika Chorób Infekcyjnych i Alergologii, Klinika Gastroenterologii i Chorób Wewnętrznych
Study officials:
affiliation: Human Biome Institute S.A.
name: Jaroslaw Bilinski, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rokkas T, Gisbert JP, Gasbarrini A, Hold GL, Tilg H, Malfertheiner P, Megraud F, O'Morain C. A network meta-analysis of randomized controlled trials exploring the role of fecal microbiota transplantation in recurrent Clostridium difficile infection. United European Gastroenterol J. 2019 Oct;7(8):1051-1063. doi: 10.1177/2050640619854587. Epub 2019 May 27.
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citation: Bilinski J, Grzesiowski P, Sorensen N, Madry K, Muszynski J, Robak K, Wroblewska M, Dzieciatkowski T, Dulny G, Dwilewicz-Trojaczek J, Wiktor-Jedrzejczak W, Basak GW. Fecal Microbiota Transplantation in Patients With Blood Disorders Inhibits Gut Colonization With Antibiotic-Resistant Bacteria: Results of a Prospective, Single-Center Study. Clin Infect Dis. 2017 Aug 1;65(3):364-370. doi: 10.1093/cid/cix252.
citation: Kelly CR, Kahn S, Kashyap P, Laine L, Rubin D, Atreja A, Moore T, Wu G. Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook. Gastroenterology. 2015 Jul;149(1):223-37. doi: 10.1053/j.gastro.2015.05.008. Epub 2015 May 15.
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