INTESTIFIX for Multidrug-resistant Enterobacteriaceae colonization (intestinal carriage) | Multidrug-resistant Enterobacteriaceae infection

Inclusion criteria

• {"criterion_text":"- 1.\tPatients aged ≥ 18 years"}
• {"criterion_text":"- 2.\tFecal colonization with an MDR-E, fulfilling the criteria for classification as 3MRGN or 4MRGN (as defined by the Robert-Koch-Institute) confirmed by a positive sample (rectal swab or stool sample) obtained within 14 days prior to study enrolment"}
• {"criterion_text":"- 3.\tPatients at risk of infection with the colonizing strain referred to in criterion 2 (based on cultural resistance testing) who already experienced at least two infections within the last 6 months or three infections within the last 12 months prior to enrolment. AND/OR Patients under moderate mid- or long-term immunosuppression, defined by ≥ 1 of the following criteria: a)\tsolid organ transplant recipients receiving ≥ 2 immunosuppressants b)\trecipients of CAR-T-cell therapy or hematopoietic stem cell transplantation either within 100 days to 2 years of CAR-T-cell/ stem cell infusion c)\tmoderate or severe primary immunodeficiency (eg, DiGeorge syndrome, Wiskott-Aldrich syndrome) d)\tUse of at least 1 of the following medications: i.\tRecent treatment with corticosteroids equivalent to prednisone ≥20 mg daily for at least 14 consecutive days, all of which must have been within the last 30 days prior to study entry OR are currently receiving ≥20 mg daily that must have been administered for at least 14 consecutive days at the time of study entry. ii.\tActive treatment causing significant immunosuppression, including alkylating agents, antimetabolites, transplant-related immunosuppressive or immunomodulatory drugs (e.g. cyclosporin A, tacrolimus, methotrexate, mycophenolat mofetil, anti-T-cell immunoglobulin, everolimus, sirolimus, ruxolitinib, basiliximab, vedolizumab, cyclophosphamide), cancer chemotherapeutic agents, TNF blockers, or immunomodulatory drugs (e.g. monoclonal antibodies, bispecific antibodies, checkpoint inhibitors, biologics, Janus kinase inhibitors) e)\tchronic kidney diseases stage (CKD-EPI stage 4 or 5) requiring chronic hemodialysis for at least 6 months f)\tHIV infection with CD4+ cell count <200/mm³ from known medical history within the past 6 months of screening."}

Exclusion criteria

• {"criterion_text":"- 1. Resistance to colistin according to EUCAST breakpoints v.12 (MIC > 2 mg/L) of the MDR-E isolate at baseline"}
• {"criterion_text":"- 7.\tPlanned selective digestive tract decolonization within 30 days following randomization"}
• {"criterion_text":"- 8.\tKnown hypersensitivity or allergy to any of the components of the study treatment"}
• {"criterion_text":"- 9.\tCurrent hospitalization in an Intensive Care Unit"}
• {"criterion_text":"- 13. Concurrent participation in another clinical trial with an investigational drug is not permitted, unless the drug under study is related to the treatment of the underlying condition or a transplantation"}
• {"criterion_text":"- 10. Current pregnancy or nursing period"}
• {"criterion_text":"- 11.\tFailure to use highly-effective contraceptive methods"}
• {"criterion_text":"- 12.\tInability to give written informed consent"}
• {"criterion_text":"- 2.\tForeseeable inability to swallow 30 FMT capsules over two days"}
• {"criterion_text":"- 3.\tActive inflammatory bowel disease (e.g. ulcerative colitis or Crohn’s disease)"}
• {"criterion_text":"- 4.\tSevere immunosuppression defined as: (a) patients with current or foreseeable neutropenia within the 14 days of study treatment (defined as <500 neutrophils/µl) (b) patients scheduled for allogeneic stem cell transplantation (SCT) or having received allogeneic SCT within the 100 days prior to study treatment (c) patients with active graft versus host disease or allograft rejection requiring intensified immunosuppressive treatment, defined as the current use of >2 immunosuppressive or immunomodulatory drugs (e.g. cyclosporin A, tacrolimus, methotrexate, mycophenolat mofetil, anti-T-cell immunoglobulin, everolimus, sirolimus, ruxolitinib, basiliximab, vedolizumab, corticosteroids or cyclophosphamide)"}
• {"criterion_text":"- 5.\tActive infection with the MDR-E organism to be eradicated"}
• {"criterion_text":"- 6.\tCurrent or scheduled administration of antibiotic treatment active against the MDR-E organism to be eradicated"}

Primary endpoints

• {"endpoint_text":"- Detectable intestinal carriage of MDR-E at day 30 in standard qualitative cultural assessment","definition_or_measurement_approach":"Detection by standard qualitative cultural assessment at day 30 (i.e. qualitative culture to detect intestinal carriage of MDR-E)."}

Secondary endpoints

• {"endpoint_text":"- •\tComparison of safety and tolerability data between groups via review of nature, frequency and severity of adverse events (AEs), serious AEs (SAEs), and new medical conditions for 30 days","definition_or_measurement_approach":"Safety/tolerability assessed by review of nature, frequency and severity of AEs, SAEs and new medical conditions for 30 days."}
• {"endpoint_text":"- •\tCharacterization of changes in bacterial and fungal intestinal microbiota community structures and taxonomic classification (α- and ß-diversity) at day 0 compared to day 4, 12, 30 and 90","definition_or_measurement_approach":"Microbiota community structure and taxonomic classification analyzed (α- and ß-diversity) at day 0 and days 4, 12, 30 and 90."}
• {"endpoint_text":"- •\tComparison of intestinal carriage of MDR-E at day 30 in quantitative cultural assessment","definition_or_measurement_approach":"Quantitative culture assessment of intestinal MDR-E carriage at day 30."}
• {"endpoint_text":"- •\tCharacterization and differences of patterns in the intestinal microbiota distribution in patients at baseline compared to day 4, 12, 30 and 90 with and without successful decolonization","definition_or_measurement_approach":"Analysis of intestinal microbiota distribution patterns at baseline and days 4, 12, 30 and 90, comparing patients with and without successful decolonization."}
• {"endpoint_text":"- •\tRate of bacterial infections until day 90","definition_or_measurement_approach":"Incidence rate of bacterial infections up to day 90."}
• {"endpoint_text":"- •\tRate of MDR-E infections until day 90","definition_or_measurement_approach":"Incidence rate of infections caused by MDR-E up to day 90."}
• {"endpoint_text":"- •\tRate of any type of infection (bacteria, viruses, fungi, parasites) until day 90","definition_or_measurement_approach":"Incidence rate of any infection (bacterial, viral, fungal, parasitic) up to day 90."}
• {"endpoint_text":"- •\tRate of hospitalization and all-cause mortality until day 90","definition_or_measurement_approach":"Incidence rate of hospitalization and all-cause mortality up to day 90."}

Germany

Earliest CTIS Part Ii Submission Date

22-04-2025

Latest Decision Or Authorization Date

09-10-2025

Processing Time Days

170

Number Of Sites

6

Number Of Participants

76

Primary sponsor

Full Name

Goethe University Frankfurt

Organisation Type

Educational Institution

Country Of Registered Address

Germany