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Intravesical administration of combined hyaluronic acid (HA) and chondroitin sulfate (CS) for the treatment of female recurrent urinary tract infections: a European multicentre nested case–control study
  1. Oriana Ciani1,2,
  2. Erik Arendsen3,
  3. Martin Romancik4,
  4. Richard Lunik5,
  5. Elisabetta Costantini6,
  6. Manuel Di Biase6,
  7. Giuseppe Morgia7,
  8. Eugenia Fragalà7,
  9. Tomaskin Roman8,
  10. Marian Bernat9,
  11. Giorgio Guazzoni10,
  12. Rosanna Tarricone1,11,
  13. Massimo Lazzeri10
  1. 1Centre for Research on Health and Social Care Management, Università Bocconi, Milan, Italy
  2. 2Evidence Synthesis & Modelling for Health Improvement, Institute of Health Research, University of Exeter Medical School, Exeter, UK
  3. 3Diaconessenhuis, Maatschap, Urologie, Leiden, The Netherlands
  4. 4Department of Urology, St. Cyril and Method University Hospital, Bratislava, Slovakia
  5. 5Department of Urology, Fakultná nemocnica s poliklinikou, Prešov, Slovakia
  6. 6Department of Surgical and Biomedical Science, University of Perugia, Urology and Andrology Clinic, Perugia, Italy
  7. 7Department of Urology, University of Catania, Catania, Italy
  8. 8Department of Urology, Jessenius School of Medicine, University Hospital, Martin, Slovakia
  9. 9FNsP, Urologicka Klinika, Nové Zámky, Slovakia
  10. 10Department of Urology, Humanitas Clinical and Research Center, Milan, Italy
  11. 11Department of Policy Analysis and Public Management, Università Bocconi, Milano, Italy
  1. Correspondence to Dr Oriana Ciani; oriana.ciani{at}


Objectives To compare the clinical effectiveness of the intravesical administration of combined hyaluronic acid and chondroitin sulfate (HA+CS) versus current standard management in adult women with recurrent urinary tract infections (RUTIs).

Setting A European Union-based multicentre, retrospective nested case–control study.

Participants 276 adult women treated for RUTIs starting from 2009 to 2013.

Interventions Patients treated with either intravesical administration of HA+CS or standard of care (antimicrobial/immunoactive prophylaxis/probiotics/cranberry).

Primary and secondary outcome measures The primary outcome was occurrence of bacteriologically confirmed recurrence within 12 months. Secondary outcomes were time to recurrence, total number of recurrences, health-related quality of life and healthcare resource consumption. Crude and adjusted results for unbalanced characteristics are presented.

Results 181 patients treated with HA+CS and 95 patients treated with standard of care from 7 centres were included. The crude and adjusted ORs (95% CI) for the primary end point were 0.77 (0.46 to 1.28) and 0.51 (0.27 to 0.96), respectively. However, no evidence of improvement in terms of total number of recurrences (incidence rate ratio (95% CI), 0.99 (0.69 to 1.43)) or time to first recurrence was seen (HR (95% CI), 0.99 (0.61 to 1.61)). The benefit of intravesical HA+CS therapy improves when the number of instillations is ≥5.

Conclusions Our results show that bladder instillations of combined HA+CS reduce the risk of bacteriologically confirmed recurrences compared with the current standard management of RUTIs. Total incidence rates and hazard rates were instead non-significantly different between the 2 groups after adjusting for unbalanced factors. In contrast to what happens with antibiotic prophylaxis, the effectiveness of the HA+CS reinstatement therapy improves over time.

Trial registration number NCT02016118.

  • Antimicrobial Resistance
  • Hyaluronic acid
  • chondroitin sulphate

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