NCT07202949
招募中
2 期
EAT-UP - Extended Antibiotic Treatment in Chronic UTI Patients; a Phase II Safety and Efficacy Trial
概览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 192
- 试验地点
- 10
- 主要终点
- Change in urinary white blood cell (WBC) count from baseline to Week 12.
概览
简要总结
Chronic Urinary Tract Infection (UTI) is a type of UTI where symptoms are constant and occur every day, unlike recurrent UTIs, which come and go with symptom-free breaks in between. Current treatment for chronic UTI within the NHS is based on recommended guidelines for recurrent UTI. The standard approach typically includes one of the following treatments:
- Long-term, prophylactic (low) dose daily antibiotic (where medication is used at low doses to try to prevent symptoms reoccurring).
- Long-term use of a urinary antiseptic (which helps keep your urine bacteria free), called methenamine hippurate.
These often do not work for people with chronic UTI, and symptoms can persist. Moreover, standard urine tests may fail to detect infections, making diagnosis and treatment more challenging.
The EAT-UP trial will investigate whether longer courses of treatment (higher) dose antibiotics combined with methenamine hippurate (a urinary antiseptic) are a more effective treatment at reducing levels of infection and symptoms than standard of care treatments (as described above).
详细描述
EAT-UP is a UK multi-centre, randomised, open label, parallel-group, superiority, interventional phase II trial, aiming to recruit 192 female participants. Participants will undergo screening to evaluate their eligibility to participate in the trial. If eligible, participants will be randomly assigned into one of two groups:
Group 1 will receive a treatment dose antibiotic in combination with the urinary antiseptic, methenamine hippurate (1 g twice daily). The treating clinician will select one of the following antibiotics based on the individual needs of the participant, such as their medical history, concomitant medications and any known allergies:
- Cefalexin (500mg four times daily), or
- Nitrofurantoin (100mg twice daily), or
- Trimethoprim (200mg twice daily)
Group 2 will receive a low-dose prophylactic antibiotic or the urinary antiseptic, methenamine hippurate. The treating clinician will select one of the following treatments based on the individual needs of the participant, such as their medical history, concomitant medications and any known allergies:
- Amoxicillin (250mg once daily), or
- Cefalexin (125mg once daily), or
- Nitrofurantoin (50mg once daily), or
- Trimethoprim (100mg once daily), or
- Methenamine Hippurate (1g twice daily)
Participants will be taking trial medication for 12 weeks and will be required to attend clinic for assessments every 4 weeks. Participant will complete questionnaires and provide blood, urine, and perineal (the area between the vagina and anus) swabs samples.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
- •A fresh urine microscopy examination showing ≥20 white blood cells/µl of urine at the screening visit.
- •Female\*\* patients.
- •Aged ≥18 years.
- •Screening blood result of eGFR ≥45ml/min/1.73m
- •Able and willing to attend trial visits and comply with all study procedures for the duration of the trial.
- •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.
排除标准
- •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.
- •Inability to take methenamine hippurate due to medical contraindications.
- •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.
- •Current use of Sodium-Glucose Transport Protein 2 (SGLT2) inhibitors\*.
- •A current diagnosis of bladder cancer.
- •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.
- •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.
- •Pregnancy (or planned pregnancy during trial participation) and/or breastfeeding.
- •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.
- •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.
研究组 & 干预措施
Treatment dose antibiotic in combination with methenamine hippurate
Experimental
干预措施: Treatment dose antibiotic in combination with methenamine hippurate (Drug)
Prophylactic dose antibiotic or methenamine hippurate monotherapy
Active Comparator
干预措施: Prophylactic dose antibiotic or methenamine hippurate monotherapy (Drug)
结局指标
主要结局
Change in urinary white blood cell (WBC) count from baseline to Week 12.
时间窗: Baseline, Week 4, Week 8, Week 12
Urinary white blood cell (WBC) count, measured using fresh urine microscopy, will be used as the principal biomarker to indicate urinary tract inflammation.
次要结局
- Changes in EuroQol EQ-5D 5-Level Health Related Quality of Life Questionnaire (EQ-5D-5L) scores at week 12, adjusted for baseline(Baseline, Week 12)
- Changes in ICIQ Lower Urinary Tract Symptoms quality of life (ICIQ-LUTSqol)(Baseline, Week 4, Week 8, Week 12)
- Changes in Whittington 39-point Lower Urinary Tract Symptoms (W-39 LUTS) scores at week 12, adjusted for baseline(Baseline, Week 4, Week 8, Week 12)
- Patient Global Impression of Improvement (PGI-I) scores at week 12.(Week 4, Week 8, Week 12)
- Participant satisfaction with medication using Lübeck Medication Satisfaction (LMS) Questionnaire scores at week 12(Week 12)
- Treatment adherence assessed by the MARS-5 questionnaire at weeks 4, 8 and 12.(Week 4, Week 8 and Week 12)
- Frequency of rescue therapy use for participants requiring further treatment escalation for an acute flare of symptoms at 12(Week 4, Week 8 and Week 12)
- Changes in urine culture species, cfu/ml count, sensitivities and resistance profiles at week 12, adjusted for baseline(Baseline and Week 12)
- Changes in Perineal swab analyses of E.coli identified, sensitivities and resistance profiles at week 12, adjusted for baseline(Baseline and Week 12)
- Safety and tolerability of the intervention as indicated by changes in pulse (bpm) from baseline to Week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in blood pressure (mmHg) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in temperature (°) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in respiratory rate (breaths per minute)from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in weight (kg) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Haemoglobin (g/dL) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Red Blood Cell Count (10^12/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Platelets (10^9/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in total White Blood Cell Count (10^9/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Neutrophils (10^9/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Lymphocytes (10^9/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Monocytes (10^9/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Eosinophils (10^9/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Basophils (10^9/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Albumin (g/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Total Bilirubin (µmol/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Alanine Transaminase (ALT) (IU/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Alkaline Phosphatase (ALP) (IU/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Calcium (mmol/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Carbon dioxide (bicarbonate) (mmol/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Chloride (mmol/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Creatinine (µmol/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Estimated Glomerular Filtration Rate (eGFR) (ml/min/1.72m²) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Glucose (mmol/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Phosphorus inorganic (phosphate) (mmol/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Potassium (mmol/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Sodium (mmol/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by changes in Urea (mmol/L) from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
- Safety and tolerability of the intervention as indicated by the occurrence / severity of treatment related Adverse Events assessed by CTCAE v5.0 from baseline to week 12(Baseline, Week 4, Week 8 and Week 12)
研究者
研究点 (10)
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