Evaluating Urinary Microbiome Modulation :An RCT of Antibiotic vs Gynoflor Prophylaxis in Postmenopausal Women With Recurrent Cystitis

Not Applicable

Recruiting

• Conditions: Recurrent Urinary Tract Infection (rUTI) Urinary Tract Infections Cystitis, Recurrent Postmenopause (Population Focus)
• Interventions: Drug: Nitrofurantoin; Drug: Gynoflor

• Registration Number: NCT07186465
• Lead Sponsor: Mahidol University

Brief Summary

This randomized controlled trial will compare two ways to prevent recurrent urinary tract infection (rUTI) in postmenopausal women: (1) nightly oral nitrofurantoin and (2) a vaginal tablet containing Lactobacillus with ultra-low-dose estriol (Gynoflor). The study also tracks how each strategy changes the urinary microbiome. Participants are randomized 1:1 in computer-generated blocks; the trial is open-label and follows patients for 6 months.

Women ≥40 years with rUTI will be enrolled. The nitrofurantoin arm takes 100 mg once nightly for 6 months. The Gynoflor arm uses one vaginal tablet nightly for 14 days, then twice weekly through month 6.

The primary outcome is the proportion with rUTI recurrence within 6 months. Secondary outcomes include time to first recurrence, antibiotic resistance among breakthrough infections, change in lower urinary tract symptoms measured by the Thai RUTISS questionnaire, Lactobacillus dominance, and microbiome diversity (qPCR and 16S rRNA).

Key assessments occur at baseline and month 6: urinalysis, urine culture, urinary microbiome sampling, and kidney function tests; participants are contacted twice weekly by phone/Line to reinforce adherence and capture symptoms/adverse events. We plan to enroll \~100 participants (50 per arm) as a pilot sized by local feasibility.

Detailed Description

Background and Rationale

Recurrent cystitis affects many postmenopausal women and diminishes quality of life. While antibiotics can prevent recurrences, long-term use may drive resistance. Vaginal Lactobacillus/estriol products may reduce rUTI and improve lower urinary tract symptoms, but head-to-head data versus antibiotic prophylaxis-especially on urinary microbiome changes-are limited. This study directly compares nightly nitrofurantoin to a Lactobacillus-containing vaginal tablet (Gynoflor) and evaluates urinary microbiome modulation.

Objectives and Outcomes

Primary outcome: rUTI recurrence proportion over 6 months (nitrofurantoin vs Gynoflor).

Secondary outcomes:

Time to first recurrence within 6 months.

Antibiotic resistance among breakthrough infections during treatment.

Change in lower urinary tract symptoms (dysuria, frequency, urgency, suprapubic pain) using RUTISS (Thai).

Microbiome stability/Lactobacillus dominance and change in microbiome diversity.

Design

Open-label, parallel-group randomized controlled trial with 1:1 block randomization by computer; follow-up is 6 months.

Population

Postmenopausal women ≥40 years with recurrent UTI per clinical assessment. Key inclusion: able to follow 6-month regimen and willing to provide consent. Key exclusion: unable to take nitrofurantoin or use the Lactobacillus/estriol vaginal tablet; planned urologic surgery within 6 months; active symptomatic UTI at enrollment; recent bacterial vaginosis (≤1 month); vulvovaginal skin disorders; history of hepatitis; history of breast/uterine/cervical cancer; abnormal vaginal bleeding; withdrawal or severe adverse event.

Interventions

Nitrofurantoin arm: 100 mg orally, once nightly for 6 months.

Gynoflor arm: one vaginal tablet nightly for 14 days, then twice weekly (e.g., Monday/Friday) through month 6.

Study Procedures and Schedule

Baseline (Day 0): informed consent; randomization; symptom assessment (RUTISS); urinalysis, urine culture, urinary microbiome sampling, and serum BUN/creatinine.

During follow-up (Months 0-6): twice-weekly contact by phone/Line to reinforce adherence, capture symptoms, and solicit adverse events.

If a participant develops symptomatic UTI, she receives standard-of-care diagnosis/treatment; urine is re-checked until clear, after which study prophylaxis continues to complete 6 months.

Month 6 visit: repeat RUTISS and laboratory testing (urinalysis, culture, urinary microbiome, BUN/Cr).

Sample handling: midstream "clean-catch" urine is processed promptly (or refrigerated ≤24 h at 4 °C when needed). Typical volumes: UA 20 ml; culture 5-10 ml; microbiome 50 ml.

Microbiome Methods

Assays will be performed at the Department of Medical Sciences: quantitative PCR to estimate Lactobacillus abundance over time, and 16S rRNA gene sequencing to assess community diversity.

Sample Size and Analysis

This pilot plans \~100 participants (50 per arm), supported by local case volume and prior effect estimates. Analyses will use STATA. Continuous variables: t-test or Wilcoxon-Mann-Whitney; categorical: chi-square or Fisher's exact; paired pre/post measures: paired t-test or Wilcoxon signed-rank. Time-to-event outcomes will be summarized descriptively.

Risks and Benefits

Expected risks are those of study drugs (e.g., nitrofurantoin GI or hypersensitivity effects; local vaginal irritation with Gynoflor), minor phlebotomy discomfort, and the time burden of questionnaires. Potential benefits include fewer rUTIs and contribution to knowledge on microbiome-guided prevention. (Per protocol materials provided to participants.)

Monitoring and Adherence

Regular reminders (phone/Line) and symptom checks occur twice weekly; medication use and adverse events are documented throughout.

Study Timeline

• Status Verified: 2025-09
• Study Start: 2025-09-11
• Study First Submitted: 2025-09-15
• Study First Submitted QC: 2025-09-15
• Last Update Submitted: 2025-09-15
• Study First Posted: 2025-09-22
• Last Update Posted: 2025-09-22
• Primary Completion: 2026-06-30
• Study Completion: 2026-08-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 100

Inclusion Criteria

• 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, attend baseline and month-6 visits, and provide urine samples.

Able to give written informed consent and comply with twice-weekly phone/Line follow-ups.

Exclusion Criteria

• Current symptomatic UTI at enrollment (may be treated and reconsidered after resolution).

Known hypersensitivity/contraindication to nitrofurantoin or to the Lactobacillus/estriol vaginal tablet (Gynoflor) or their excipients; significant renal impairment/other label 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 that would preclude 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nitrofurantoin Prophylaxis	Nitrofurantoin	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.
Gynoflor Vaginal Tablet	Gynoflor	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.

Primary Outcome Measures

Name	Time	Method
Proportion of participants with recurrent UTI within 6 months	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.

Secondary Outcome Measures

Name	Time	Method
Time to first recurrent UTI	Baseline to 6 months	Days from randomization to first symptomatic, culture-confirmed UTI during the 6-month period; participants without an event are censored at 6 months.
Antibiotic resistance among breakthrough infections	During the 6-month prophylaxis period	Proportion of bacterial isolates from breakthrough UTIs that are non-susceptible to commonly tested antibiotics per local microbiology reporting.
Change in lower urinary tract symptom score (RUTISS, Thai)	Baseline and month 6	Difference in RUTISS total score from baseline to month 6 (higher scores indicate worse symptoms).
Lactobacillus abundance by qPCR	Baseline and month 6	Change in Lactobacillus copy number/relative abundance in midstream urine measured by quantitative PCR.
Urinary microbiome diversity by 16S rRNA sequencing	Baseline and month 6	Change in alpha-diversity indices of urine microbiota profiles determined by 16S rRNA gene sequencing.
Incidence of adverse events related to intervention	Up to 6 months	Number and proportion of participants with any intervention-related adverse event
Adherence to assigned prophylaxis	During 6 months	Proportion of scheduled doses taken, assessed by medication logs and twice-weekly contacts

Trial Locations

Locations (1)

Faculty of Medicine Ramathibodi Hospital Mahidol University; 🇹🇭 Bangkok, Phayatai Ratchathewi, Thailand