FEMITRANS

Rate of new UTI episodes within 180 days after treatment. A UTI for the endpoint assessment is defined as presence of at least one typical symptom (dysuria, alguria, pollakiuria or flank pain) in the absence of alternative causes plus the detection of a typical or potential uropathogen as defined by protocol by urinary culture.

• Time to Post-FMT UTI: time to first UTI episode after treatment
• Symptom burden: mean changes in ACSS score values on Day 7, 30, 90 and 180 compared to Baseline.
• Quality of Life: mean changes in score values on Day 30, 90 and 180 compared to Baseline
• Number of new UTI episodes within 180 days after treatment caused by the same uropathogen as determined by whole genome sequencing
• Antibiotic treatment frequency: Number of rUTI episodes treated with antibiotic until day 180
• Vaginal infections: Number of bacterial vaginosis and candidosis until day 180
• Assessment of safety: comparison of safety data between patients with or without FMT via review of nature, frequency and severity of adverse events (AEs), serious AEs (SAEs), and new medical conditions during six-month follow-up period

 Exploratory endpoints:

• Post-FMT microbiota composition: vaginal, urinary and intestinal microbiota changes in women with rUTI up to 180 days after FMT relative to baseline (before FMT)
• Post-FMT donor microbiota engraftment: detection of donor-derived strains in the intestinal and/or vaginal and urinary microbiota of women with rUTI after FMT
• Pre-FMT microbiota overlap: detection of person-specific shared microbial strain reservoirs between the urinary, vaginal and gastrointestinal microbiota of women with rUTI 
• Donor strain engraftment prediction: validation of algorithm to predict post-FMT microbiota assembly based on pre-FMT patient and donor microbiota composition
• Cost-efficiency: assessment of 16S rRNA gene amplicon sequencing as alternative to metagenomic sequencing to determine microbiota compositions for predictive algorithm
• Uropathogen tracking/typing: determination of relative abundance and antimicrobial susceptibility profiles of the initially identified causative uropathogen strain in urinary, vaginal and gastrointestinal microbiota up to 180 days after FMT relative to baseline
• Impact of rUTI history (time since first diagnosis, frequency, prior treatments) and risk factors (drinking quantity, new sexual partner, method of contraception, presence of multi-drug resistant organisms) on rate of new UTI episodes within 180 days after treatment

 Typical or potential uropathogens include: Enterobacterales, Pseudomonas aeruginosa, Staphylococcus saprophyticus, Group A and B Streptococcus spp., Staphylococcus aureus, Enterococcus spp., Aerococcus sanguinicola.

• Premenopausal adult women with recent history of rUTI defined as ≥ four UTI during the last 12 months. A UTI is defined as presence of at least one typical symptom (dysuria, alguria, pollakiuria or flank pain) in the absence of alternative causes.
• Unsuccessful secondary prophylaxis of rUTI by lifestyle modifications including increased water intake and postcoital voiding 
• Last acute symptomatic UTI episode confirmed by urinary culture and caused by either Escherichia coli or Klebsiella pneumoniae susceptible to fosfomycin
• Written informed consent obtained according to international guidelines and local laws
• Ability to understand the nature of the trial and the trial related procedures and to comply with them

• Inability to swallow 30 FMT capsules and undergo bowel lavage
• Known anatomical or functional abnormalities in the lower urinary tract including neurogenic bladder and incontinence
• Modifiable risk factors for rUTI (e.g. uncontrolled diabetes mellitus)
• Current pregnancy
• Uncontrolled inflammatory bowel disease (e.g. ulcerative colitis or Crohn's disease) defined as the necessity to start or modify immunosuppressive treatment within the preceding three months due to disease activity.
• Presence of severe intestinal inflammation due to other cause
• Advanced stage chronic heart failure (NYHA III/IV)
• Gastrointestinal perforation, obstruction, ileus or retention of gastric contents
• Severe immunosuppression defined as at least one of the following:

(a) patients with current or foreseeable neutropenia within the 14 days of study treatment (defined as <500 neutrophils/ml)

(b) patients scheduled for or having received CAR-T-cell therapy or allogeneic stem cell transplantation (SCT) or solid organ transplantation within 100 days prior or after enrolment

(c) patients with active graft versus host disease or allograft rejection requiring intensified immunosuppressive treatment

(d) patients treated with corticosteroids equivalent to prednisone ≥20 mg daily for 14 consecutive days prior or after enrollment

(e) patients with HIV infection with CD4+ cell count <200/mm³ within the past 3 months of screening

• Known allergy, hypersensitivity or intolerance to any of the used investigational medicinal products
• Planned or ongoing intake of prohibited concomitant medication as per protocol
• Currently enrolled in another interventional trial
• Failure to use one of the following safe methods of contraception: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception; e.g. Women can only take part in this study if the risk of becoming pregnant is absolutely minimized. Save contraceptive methods comprise: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception and have to be used while participating in the study; (see section 7.5.3).
• Other conditions that according to the investigator might interfere with the evaluation of study objectives or patient safety.

Fecal microbiota transfer (FMT)