EAT-UP - Extended Antibiotic Treatment in chronic UTI Patients; a Phase II safety and efficacy trial
Chronic urinary tract infection
Participants will be recruited and randomly allocated (via an online web-based randomisation service called Sealed Envelope) to one of two treatment arms in a 1:1 ratio: Arm A (Experimental): Treatment dose antibiotic in combination with methenamine hippurate Arm A includes treatment with one of three treatment dose antibiotic options, selected by the treating clinician, in combination with methenamine hippurate. Participants allocated to this arm will receive combination therapy, consisting of one of the following antibiotics: 1. Cefalexin (500 mg four times daily), or 2. Nitrofurantoin (100 mg twice daily), or 3. Trimethoprim (200 mg twice daily) in combination with Methenamine Hippurate (1 g twice daily) for 12 weeks. Arm B (Active Comparator): Prophylactic dose antibiotic or methenamine Hippurate monotherapy Arm B includes treatment with one of four prophylactic dose antibiotics or methenamine hippurate, but not both, selected by the treating clinician. Participants in this arm will receive monotherapy of one of the following: 1. Amoxicillin (250 mg once daily), or 2. Cefalexin (125 mg once daily), or 3. Nitrofurantoin (50 mg once daily), or 4. Trimethoprim (100 mg once daily), or 5. Methenamine hippurate (1 g twice daily) for 12 weeks. All treatment will be taken orally. Participants will be followed up every 4 weeks while taking trial medication.
Current key inclusion criteria as of 05/02/2026: 1. A diagnosis of chronic UTI, without structural or functional urinary tract abnormality*, defined as daily persistent symptoms affecting storage (urinary frequency, urgency or urge incontinence) and urinary tract pain symptoms (including bladder pain, urethral pain, or dysuria), for at least 3 months prior to the screening visit, with previously associated transient symptomatic improvement to antibiotic treatment for UTI, which in the opinion of the delegated clinician is secondary to chronic urinary tract infection. 2. A fresh urine microscopy examination showing ≥20 white blood cells/µl of urine at the screening visit. 3. Female** patients. 4. Aged ≥18 years. 5. Screening blood result of eGFR ≥45ml/min/1.73m2. 6. Able and willing to attend trial visits and comply with all study procedures for the duration of the trial. 7. Able and willing to provide informed consent prior to any study related assessments and/or procedures. * A structural or functional abnormality may include kidney reflux, current or long-term catheter use, renal transplant, diversion surgery, renal stones, grade 2 or above utero-vaginal prolapse or incomplete bladder emptying. ** For the purposes of this trial, a female will be defined as an individual assigned female at birth who has a female urinary tract. _____ Previous key inclusion criteria: 1. A diagnosis of chronic UTI, without structural or functional urinary tract abnormality*, as defined as daily persistent symptoms affecting storage (urinary frequency, urgency or urge incontinence) and urinary tract pain symptoms (including bladder pain, urethral pain, or dysuria), for at least 3 months, with previously associated transient symptomatic improvement to antibiotic treatment for UTI, which in the opinion of the delegated clinician is secondary to chronic urinary tract infection 2. A fresh urine microscopy examination showing ≥20 white blood cells/µl of urine at the screening visit
Current key exclusion criteria as of 05/02/2026: 1. Inability to take at least one of the following antibiotics: Cefalexin, Nitrofurantoin, or Trimethoprim, at prophylactic and treatment dose according to NICE guidelines, and/or the Summary of Product Characteristics (such as hepatic or renal dysfunction), or any other medical contraindications. 2. Inability to take methenamine hippurate due to medical contraindications. 3. Current use of immune-modulating drugs for the treatment of chronic illnesses such as rheumatoid arthritis, chronic lung disease, any other autoimmune conditions or cancer. 4. Current use of Sodium-Glucose Transport Protein 2 (SGLT2) inhibitors*. 5. A current diagnosis of bladder cancer. 6. A diagnosis of an active sexually transmitted infection or a recent diagnosis of a sexually transmitted infection within the last 3 months of the screening visit. 7. Previous use of an antibiotic at treatment dose as per NICE guidelines for more than 14 consecutive days for treatment of UTI in the last 3 months prior to the screening visit. 8. Pregnancy (or planned pregnancy during trial participation) and/or breastfeeding. 9. Women of childbearing potential that are unable/unwilling to use an acceptable method of contraception (as described in section 3.4.1) to avoid pregnancy for the duration of the trial and for 1 week after the last dose of trial medication. 10. Current participation in another clinical trial of a device, interventional medicinal product, advanced therapy, or surgical procedure; or previous participation within 6 months of the screening visit. 11. Any medical condition or previous treatment which in the investigator’s opinion compromises the potential participant’s ability to participate. *Patient’s must not have taken a Sodium-Glucose Transport Protein 2 (SGLT2) inhibitor within 24 hours before the screening visits to be eligible for the trial. _____ Previous key exclusion criteria: 1. Inability to take at least one of the foll