Introduction
Materials and methods
Study eligibility criteria
Search strategy
Study selection and data collection
Risk of bias assessment
Data synthesis and analysis
Results
Study selection
Study characteristics
Reference | Study design | Patients | Intervention | Comparator | Primary outcome(s) | Key efficacy results | Safety |
---|---|---|---|---|---|---|---|
Constantinides et al. [18] | Nonrandomized, noncontrolled study of HA in the prevention of RUTIs | Women aged 18–45 years (mean age 35 years) with a history of RUTIs (n = 40) | HA (Cystistat®) 40 mg in 50 mL of PBS once weekly for 4 weeks, then once monthly for 4 months, followed for a further 7 months | Retrospective review of patient records from before HA treatment (mean duration 15.8 months) | Mean rate of UTI per patient-year; median time to first recurrence | Mean rate of UTI per patient-year before HA 4.3 vs after HA 0.3 (p < 0.001); median time to recurrence before HA 96 days vs after HA 498 days (p < 0.001) | No serious AEs: 9 cases of mild bladder irritation after instillation, 3 patients required anti-inflammatory medication |
Lipovac et al. [17] | Nonrandomized, noncontrolled study of HA in the prevention of RUTIs | Women aged 17–34 years (mean age 28 years) with a history of RUTIs (n = 20) | HA (Cystistat®) 40 mg in 50 mL of PBS once weekly for 4 weeks, then once monthly for 5 months, followed for a further 6 months | Retrospective review of patient records from before HA treatment (mean duration 36 weeks) | Mean rate of UTI per patient-year; mean time to first recurrence | Mean rate of UTI per patient-year before HA 4.99 vs after HA 0.56 (p < 0.001); mean time to recurrence before HA 76.7 days vs after HA 178.3 days (p < 0.001) | No serious AEs: 18 cases of mild to moderate pain during instillation, 6 cases of cramping/burning, 3 required anti-inflammatory medication |
Damiano et al. [22] | Randomized, double-blind, placebo-controlled study of HA-CS in the prevention of RUTIs | Women (mean age 35 years) with a history of RUTIs (n = 57) | 50 mL of HA 1.6% plus CS 2.0% solution (Ialuril®) once weekly for 4 weeks, then once monthly for 5 months, followed for 12 months in total (n = 28) | 50-mL placebo (saline) administered with the same schedule, followed for 12 months in total (n = 29) | Mean number of UTIs per patient-year | Mean number of UTIs per patient-year in HA-CS group 0.67 vs in placebo group 4.19 (p < 0.001) | No serious AEs: 3 cases of moderate urinary storage symptoms with HA-CS (vs none with placebo), 1 patient required anti-inflammatory medication |
Centemero et al. [19] | Nonrandomized, noncontrolled study of HA in the prevention of RUTIs | Women aged 25–48 years (mean age 37 years) with a history of RUTIs (n = 48) | HA (Cystistat®) 40 mg in 50 mL of PBS once weekly for 8 weeks, followed for 18 months in total | Retrospective review of patient records from before HA treatment | Mean time to UTI recurrence | Mean time to UTI recurrence before HA 39.85 days vs after HA 190.64 days (p < 0.001) | No serious AEs |
De Vita and Giordano. [23] | Randomized, controlled study of HA-CS in the prevention of RUTIs | Women (mean age 60 years) with a history of RUTIs (n = 28) | HA 800 mg plus CS 1 g (Ialuril®) in 50 mL of saline solution once weekly for 4 weeks, then once every 2 weeks for 4 weeks, followed for 12 months in total (n = 12) | SMX 200 mg plus TMP 40 mg once weekly for 6 weeks, followed for 12 months in total (n = 14) | Mean number of UTI after 2 and 12 months’ follow-up | Mean number of UTIs after 2 months in the HA-CS group 3 vs in the control group 2.9; after 12 months in the HA-CS group 1 vs in the control group 2.3 (p = 0.02) | No AEs |
Cicione et al. [21] | Multicenter, retrospective, nonrandomized, noncontrolled (observational) study of HA-CS in the prevention of RUTIs | Women (mean age 53 years) with a history of RUTIs (n = 157) | 50 mL of HA 1.6% plus CS 2% (Ialuril®) once weekly for 4 weeks, then once monthly for 5 months, followed for up to 24 months | Retrospective review of patient records before HA-CS treatment (12 months) | Mean number of UTIs per patient-year; mean time to UTI recurrence | Mean number of UTIs per patient-year before HA-CS 4.13 vs after HA-CS 0.44 (p = 0.01); mean time to UTI recurrence before HA-CS 94.8 days vs after HA-CS 178.4 days (p = 0.01) | 10 cases of moderate urinary storage symptoms (moderate pain after instillation), 1 patient required medication for symptom relief |
Gugliotta et al. [24] | Multicenter, retrospective, cohort study of HA-CS in the prevention of RUTIs | Women (mean age 38 years) with a history of RUTIs (n = 174) | HA 1.6% plus CS 2% (Ialuril®) in 50 mL of water plus calcium chloride once weekly for 4 weeks, then once monthly for 4 months, followed for a further 12 months (n = 98) | SMX 200 mg plus TMP 40 mg once daily for 6 weeks, followed for a further 12 months (n = 76) | Total number of UTIs recorded over 12 months; percentage of patients UTI-free at 12 months | At 12 months, total number of UTIs in the HA-CS group 69 vs in the control group 109; percentage of patients UTI-free, in the HA-CS group 36.7% vs in the control group 21.0% (p = 0.03) | No serious AEs; 78% of patients reported mild/moderate pain or burning during instillation, 22 patients required anti-inflammatory medication |
Ciani et al. [20] | Multicenter, retrospective, case–control study of HA-CS in the prevention of RUTIs | Women aged 18–75 years (mean age 53 years) with a history of RUTIs (n = 276) | HA 1.6% plus CS 2.0% (Ialuril®) once weekly for 4 weeks, then once every 2 weeks for 4 weeks and once monthly thereafter (different patterns used; a maximum of 7 installations; n = 181) | Standard of care prophylaxis (antimicrobial, immunoactive, probiotics, cranberry or a combination; n = 95) | Objective UTI recurrence within 12 months of treatment | Bacteriologically confirmed UTI in the HA-CS group 55.7% of patients vs in control group 62.1% of patients (p = 0.313) | Not reported |