Evaluating Urinary Microbiome Modulation :An RCT of Antibiotic vs Gynoflor Prophylaxis in Postmenopausal Women With Recurrent Cystitis
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Proportion of participants with recurrent UTI within 6 months
研究概览
简要总结
This open-label, parallel-group randomized controlled trial compares two prophylaxis strategies for recurrent urinary tract infection (rUTI) in postmenopausal women: (1) nightly oral nitrofurantoin 100 mg for 6 months versus (2) a vaginal tablet containing Lactobacillus with ultra-low-dose estriol (Gynoflor: nightly for 14 days, then twice weekly to month 6). Participants (≥40 years) are randomized 1:1 in computer-generated blocks and followed for 6 months. The primary endpoint is the proportion with rUTI recurrence within 6 months. Secondary endpoints include time to first recurrence, antibiotic resistance in breakthrough infections, change in lower urinary tract symptoms (Thai RUTISS), and urinary microbiome measures (Lactobacillus dominance and community diversity by qPCR and 16S rRNA). Key assessments occur at baseline and month 6 (urinalysis, culture, urinary microbiome sampling, and kidney function). Adherence and adverse events are captured via twice-weekly phone/Line contacts. Approximately 100 participants (50 per arm) will be enrolled as a feasibility-sized pilot.
详细描述
Background and Rationale
Recurrent cystitis is common after menopause and burdens quality of life and healthcare use. Antibiotic prophylaxis is effective but may promote antimicrobial resistance with long-term use. Vaginal Lactobacillus with ultra-low-dose estriol can restore urogenital flora and potentially reduce rUTI and lower urinary tract symptoms. Comparative data versus nightly antibiotic prophylaxis-and effects on the urinary microbiome-remain limited. This trial directly evaluates clinical recurrence and microbiome modulation with nitrofurantoin versus a Lactobacillus/estriol vaginal tablet over 6 months.
Objectives
Primary objective: Compare the 6-month rUTI recurrence proportion between nitrofurantoin and Gynoflor.
Key secondary objectives: (a) time to first recurrence; (b) antimicrobial resistance patterns in breakthrough infections; (c) change in Thai RUTISS score; (d) Lactobacillus dominance and within-sample diversity of the urinary microbiome.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
盲法说明
Open-label study; no masking of participants, care providers, investigators, or outcomes assessors. Allocation is revealed at randomization. Blinding is not feasible because the interventions differ in route and schedule (oral nitrofurantoin vs vaginal Lactobacillus/estriol). Laboratory analyses (urine culture, qPCR, 16S rRNA) use coded sample IDs to reduce bias, but allocation could be accessed if needed; therefore the study is unblinded.
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female, postmenopausal, age ≥40 years
- •Clinical history of recurrent urinary tract infection (rUTI) as assessed by the investigator
- •Able and willing to take assigned prophylaxis for 6 months
- •Able to attend baseline and Month 6 study visits and provide urine samples
- •Able to provide written informed consent
- •Willing and able to complete twice-weekly phone/LINE follow-ups
排除标准
- •Current symptomatic UTI at enrollment (may be treated and reconsidered after resolution)
- •Known hypersensitivity or contraindication to nitrofurantoin or to the Lactobacillus/estriol vaginal tablet (Gynoflor) or their excipients; significant renal impairment or other label-based contraindications to nitrofurantoin per local practice
- •Planned urologic surgery or procedure expected during the 6-month study period
- •Recent bacterial vaginosis (e.g., within the past month) or active vulvovaginal skin disorders precluding vaginal product use
- •History of hormone-dependent malignancy (e.g., breast, uterine, or cervical cancer) or unexplained abnormal vaginal bleeding
- •Significant liver disease (e.g., active hepatitis) or other conditions judged by the investigator to make participation unsafe
- •Participation in another interventional trial that could interfere with outcomes
- •Withdrawal of consent or severe adverse event requiring discontinuation
研究组 & 干预措施
Nitrofurantoin Prophylaxis
Nightly oral nitrofurantoin 100 mg for 6 months as prophylaxis for recurrent UTI in postmenopausal women. If symptomatic UTI occurs, treat per standard care and, once resolved, continue assigned prophylaxis to complete 6 months. Monitoring per protocol: baseline and month-6 visits with urinalysis, urine culture, urinary microbiome, and kidney function; twice-weekly phone/Line check-ins for adherence, symptoms, and adverse events.
干预措施: Nitrofurantoin (Drug)
Gynoflor Vaginal Tablet
Vaginal tablet containing Lactobacillus with ultra-low-dose estriol (Gynoflor) for 6 months: insert 1 tablet nightly for 14 days, then twice weekly through month 6. Same monitoring and management as comparator: if UTI occurs, treat per standard care and then resume assigned prophylaxis to finish 6 months.
干预措施: Gynoflor (Drug)
结局指标
主要结局
Proportion of participants with recurrent UTI within 6 months
时间窗: Baseline to 6 months after randomization
Number of participants who experience ≥1 episode of symptomatic urinary tract infection (UTI) during the 6-month prophylaxis period, confirmed by clinical symptoms and positive urine culture per hospital standard. Event counted once per participant; groups compared between arms.
次要结局
- Adherence to assigned prophylaxis(During 6 months)
- Antibiotic resistance among breakthrough infections(During the 6-month prophylaxis period)
- Time to first recurrent UTI(Baseline to 6 months)
- Change in lower urinary tract symptom score (RUTISS, Thai)(Baseline and month 6)
- Lactobacillus abundance by qPCR(Baseline and month 6)
- Urinary microbiome diversity by 16S rRNA sequencing(Baseline and month 6)
- Incidence of adverse events related to intervention(Up to 6 months)