Study to Evaluate the Efficacy of Lactobacillus Crispatus M247 in the Prevention of Recurrent Urinary Tract Infections

Oral Lactobacillus Crispatus M247 as an Add-on to Enterococcus Faecium L3 and Bifidobacterium Animalis Subsp. Lactis BB-12 for the Prevention of Recurrent Urinary Tract Infections in Women: A Prospective Randomized Controlled Trial

This randomized, open-label, controlled clinical trial evaluates the efficacy and safety of Lactobacillus crispatus M247 (CRISPACT®) in preventing recurrent urinary tract infections (rUTIs) in women. The study enrolls 84 adult female participants with a history of recurrent UTIs, defined as ≥3 episodes in the past year or ≥2 episodes in the past six months. Participants are randomized into two groups: the Probiotic Group, receiving iNatal Duo® (containing Bifidobacterium animalis subsp. lactis BB-12 and Enterococcus faecium L3) for 30 days plus CRISPACT® (Lactobacillus crispatus M247) administered orally for 90 days; and the Control Group, receiving iNatal Duo® alone for 30 days without additional probiotic supplementation. The primary outcome is the reduction in the frequency of rUTIs over 12 months, while secondary outcomes include symptom improvement, quality of life, and safety assessments.

Recurrent urinary tract infections (rUTIs) represent a significant public health issue, disproportionately affecting women with hormonal fluctuations, sexual activity-related risks, or prior antibiotic exposure. Standard treatment relies on antibiotic therapy, which, while effective, contributes to antimicrobial resistance, microbiota imbalance, and increased recurrence risk. Probiotics, particularly Lactobacillus crispatus, have demonstrated potential in restoring urogenital microbiota balance and reducing uropathogen overgrowth.

This study aims to assess whether CRISPACT® (Lactobacillus crispatus M247), administered orally, provides superior protection against rUTIs compared with standard care using iNatal Duo® alone. The study follows a randomized, controlled design with 84 participants allocated to two parallel arms. The Probiotic Group receives iNatal Duo® for 30 days combined with CRISPACT® for 90 days, while the Control Group receives iNatal Duo® alone for 30 days without additional probiotic supplementation.

The primary objective is to evaluate the reduction in rUTI recurrence over a 12-month follow-up period, assessed through clinical diagnosis and patient-reported data. Secondary objectives include evaluation of symptom relief, patient-reported quality-of-life outcomes (EQ-5D, King's Health Questionnaire), and safety and tolerability of the probiotic intervention. The study seeks to provide clinical evidence supporting probiotic-based strategies for rUTI prevention and reduction of antibiotic dependence.

Inclusion Criteria:

• Adult women aged 18-65 years.
• History of recurrent urinary tract infections (rUTIs), defined as ≥3 episodes in the past year or ≥2 episodes in the past 6 months.
• Able to provide informed consent and comply with study procedures.

Exclusion Criteria:

• Age <18 years.
• Ongoing complicated cystitis or uncomplicated pyelonephritis.
• History of urological abnormalities or kidney stones.
• Recent sexually transmitted infection or bacterial vaginosis, or history of recurrent bacterial vaginosis.
• Risk factors for sexually transmitted diseases.
• Ongoing pregnancy, planning pregnancy, or breastfeeding.
• Diagnosis of diabetes mellitus.
• Diagnosis of HIV infection or other immunocompromised states.
• Recent history of drug or alcohol abuse.
• Persistent symptoms and/or pyuria after acute UTI treatment.
• Uterine, cervical, vaginal, or urethral cancer.
• Urethral diverticulum.
• Tuberculous, radiation-induced, cyclophosphamide-induced, or chemical cystitis.
• Benign or malignant bladder tumors.
• Recent diagnosis of vaginitis.
• Known hypersensitivity to study products.
• Failure to provide informed consent.