Recurrent Urinary Tract Infection
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DIETARY_SUPPLEMENTLactobacillus crispatus M247
CRISPACT® (Lactobacillus crispatus M247), PharmExtracta S.p.A
DIETARY_SUPPLEMENTiNatal-Duo® (containing Bifidobacterium animalis subsp. lactis BB-12 and Enterococcus faecium L3)
iNatal-Duo®, PharmExtracta S.p.A
Sponsors
Liaquat University of Medical & Health Sciences
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
This is a randomized, controlled, open-label study assessing the efficacy of Lactobacillus crispatus M247 (CRISPACT®) in preventing recurrent urinary tract infections (rUTIs) in women with a history of recurrent UTIs. Participants are assigned to either the Probiotic Group, receiving CRISPACT® plus iNatal Duo®, or the Control Group, receiving iNatal Duo® alone. The primary outcome is the number of rUTI episodes during the 12-month follow-up period.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative number of symptomatic UTI recurrences per participant | 12 months | Cumulative number of investigator-confirmed, urine-culture-supported symptomatic UTI recurrences experienced by each participant from randomization through the 12-month follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in urinary symptoms (King's Health Questionnaire) | Baseline, 3 months | Assessment using the King's Health Questionnaire (KHQ), a validated condition-specific questionnaire for urinary symptoms. Scores range from 0 to 100, with higher scores indicating worse symptom severity and impact on quality of life. |
| Pelvic pain and urgency/frequency symptom burden at month 3 | 3 months | Assessment using the Pelvic Pain and Urgency/Frequency (PUF) questionnaire. Total scores range from 0 to 35, with higher scores indicating greater symptom severity. |
| Change in health-related quality of life (EQ-5D) | Baseline, 3 months | Assessment using the EuroQol 5-Dimension questionnaire (EQ-5D). The individual health dimensions and perceived health status were assessed separately. |
| Change in sexual function | Baseline, 3 months | Assessment using the Female Sexual Function Index-6 (FSFI-6). The available sexual-health measures were assessed separately. |
| Treatment adherence | 3 months | Proportion of participants taking at least 90% of the scheduled doses of the assigned probiotic supplementation, assessed using participants' treatment diaries and counts of returned unused sachets. |
| Treatment tolerability | 3 months | Participants' overall assessment of treatment tolerability, categorized as excellent, good, fair, or poor, together with the number of treatment discontinuations. |
| Safety and adverse events | 12 months | Number and proportion of participants experiencing adverse events, serious adverse events, vaginitis, bacterial vaginosis, or other genital infections during the study. |
| Cumulative number of symptomatic UTI recurrences per participant through month 3 | 3 months | Cumulative number of investigator-confirmed, urine-culture-supported symptomatic UTI recurrences experienced by each participant from randomization through the 3-month assessment. |
| Participants experiencing at least one symptomatic UTI recurrence through month 3 | 3 months | Number and proportion of participants experiencing at least one investigator-confirmed, urine-culture-supported symptomatic UTI recurrence from randomization through the 3-month assessment. |
| Participants experiencing at least one symptomatic UTI recurrence through month 12 | 12 months | Number and proportion of participants experiencing at least one investigator-confirmed, urine-culture-supported symptomatic UTI recurrence from randomization through the 12-month assessment. |
| Participants requiring culture-guided antibiotic therapy for a symptomatic UTI recurrence | 12 months | Number and proportion of participants experiencing at least one investigator-confirmed, urine-culture-supported symptomatic UTI recurrence whose symptoms did not improve to a clinically meaningful extent within 3 days of an initial non-antibiotic regimen. This regimen comprised oral D-mannose 500 mg three times daily, taken after voiding and away from meals, together with ibuprofen 400 mg once daily in the morning after breakfast, with a second 400-mg dose 12 hours later when required. Participants reporting an allergy to ibuprofen received paracetamol 1,000 mg once daily, with a second 1,000-mg dose 12 hours later when required. Participants without clinically meaningful improvement by day 3 received antibiotic therapy selected according to urine-culture and antimicrobial-susceptibility results. The denominator was the number of participants experiencing at least one confirmed recurrence; each participant was counted only once if antibiotic therapy was required for any recurrence. |
Countries
Italy
Outcome results
None listed