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

Oriana Ciani, Erik Arendsen, Martin Romancik, Richard Lunik, Elisabetta Costantini, Manuel Di Biase, Giuseppe Morgia, Eugenia Fragalà, Tomaskin Roman, Marian Bernat, Giorgio Guazzoni, Rosanna Tarricone, Massimo Lazzeri, Oriana Ciani, Erik Arendsen, Martin Romancik, Richard Lunik, Elisabetta Costantini, Manuel Di Biase, Giuseppe Morgia, Eugenia Fragalà, Tomaskin Roman, Marian Bernat, Giorgio Guazzoni, Rosanna Tarricone, Massimo Lazzeri

Abstract

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.

Keywords: Antimicrobial Resistance; Hyaluronic acid; chondroitin sulphate.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Figures

Figure 1
Figure 1
Flow diagram describing numbers of individuals at each stage of study. HA+CS, hyaluronic acid and chondroitin sulfate.

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