Microbiome-Modulating Prophylaxis RCT: Antibiotic vs Gynoflor in Postmenopausal Women With Recurrent Cystitis

NCT07186465 | Recruiting Phase 4 DMC

• 2 other identifiers: MURA2024/339Ref.2024/671
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cystitis, Recurrent; Urinary Tract Infections

Keywords

Postmenopausal Women; Nitrofurantoin; Antibiotic Prophylaxis; Gynoflor; Lactobacillus; Estriol; Vaginal Probiotics; Urinary Microbiome; 16S rRNA Sequencing; qPCR; Lower Urinary Tract Symptoms; RUTISS Questionnaire; Adherence Monitoring; Antimicrobial Resistance; Thailand

Outcome Measures

Primary Outcomes (1)

• Proportion of participants with recurrent UTI within 6 months

  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.

  Baseline to 6 months after randomization

Secondary Outcomes (7)

• Time to first recurrent UTI

  Baseline to 6 months

• Antibiotic resistance among breakthrough infections

  During the 6-month prophylaxis period

• 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

Study Arms (2)

Nitrofurantoin Prophylaxis

ACTIVE COMPARATOR

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.

Drug: Nitrofurantoin

Gynoflor Vaginal Tablet

EXPERIMENTAL

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.

Drug: Gynoflor

Interventions

Nitrofurantoin DRUG

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.

Also known as: Nitrofurantoin macrocrystals/monohydrate

Nitrofurantoin Prophylaxis

Gynoflor DRUG

Vaginal tablet containing Lactobacillus with ultra-low-dose estriol. Insert 1 tablet nightly for 14 days, then twice weekly through month 6 as prophylaxis against recurrent urinary tract infection. If a symptomatic UTI occurs, treat per standard of care; after resolution, continue assigned prophylaxis to complete 6 months. Monitoring identical to comparator.

Also known as: Vaginal Lactobacillus with ultra-low-dose estriol

Gynoflor Vaginal Tablet

Eligibility Criteria

• Age: 40 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mahidol University: lead

Study Sites (1)

Faculty of Medicine Ramathibodi Hospital Mahidol University

Bangkok, Phayatai Ratchathewi, 10400, Thailand

RECRUITING

MeSH Terms

Conditions

Cystitis; Recurrence; Urinary Tract Infections; Lower Urinary Tract Symptoms

Interventions

Nitrofurantoin

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections; Urological Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitrofurans; Nitro Compounds; Organic Chemicals; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Lappanawat Santitham

CONTACT

+66944314994; cambellabios@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, two-arm, parallel-group, open-label trial in postmenopausal women with recurrent UTI. Participants are allocated 1:1 by computer-generated block randomization to: (a) nitrofurantoin 100 mg orally at bedtime for 6 months, or (b) Gynoflor vaginal tablet nightly for 14 days then twice weekly through month 6. Baseline and month-6 clinic visits with labs/microbiome sampling; twice-weekly remote check-ins for adherence, symptoms, and AEs. If symptomatic UTI occurs, treat per standard care and then continue assigned prophylaxis to complete 6 months.

Study Record Dates

• First Submitted: September 15, 2025
• First Posted: September 22, 2025
• Study Start: September 11, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): August 30, 2026
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Available beginning 12 months after the primary results are published (or 24 months after database lock, whichever comes first) and for 5 years thereafter.
• Access Criteria: Qualified researchers may request access by emailing the study PI/central contact with: (1) a brief proposal and analysis plan, (2) documentation of ethics/IRB approval or exemption, and (3) a signed Data Use Agreement. Requests will be reviewed by the study steering team. Approved users will receive data via secure transfer; re-identification attempts and onward sharing are prohibited, and publications must acknowledge the original study.

Locations

TH (1)