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Randomized, placebo-controlled, double-blinded study of prophylactic cranberries use in women with recurrent uncomplicated cystitis

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World Journal of Urology Aims and scope Submit manuscript

Abstract

Background

Τhe adherence of p-fimbriated Escherichia coli (E. coli) to urothelial cells leading to recurrent urinary tract infections (rUTIs) may be prevented by proanthocyanidins (PACs) contained in American cranberries.

Purpose

The purpose of this clinical trial was to assess the clinical utility of prophylactic use of high-dose PACs daily in women with a history of rUTIs.

Materials and methods

172 adult women with a history of rUTIs, defined as ≥ 2 within a 6-month period or ≥ 3 within a 12-month period were enrolled and randomized in two groups to receive either Cysticlean™ 240 mg or placebo for a 12-month period. Urine samples, vaginal and rectal swabs were collected at initial and quarterly study visits. The primary study endpoints were the number of urinary tract infections (UTIs) and changes in Quality of Life (QoL), assessed by the 36-Item Short Form Survey (SF-36) questionnaire.

Results

160 adult women of median age 40 years old (range 19–82) were finally analyzed in this randomized, placebo-controlled, double-blinded clinical trial. In response to intervention, the number of UTIs was significantly lower (Incidence rate ratio IRR 0.49, p < 0.001) and QoL was slightly improved. The numbers of E. coli isolates detected in vaginal (IRR 0.71, p value < 0.001) and in rectal swabs (IRR 0.87, p value < 0.001) were also significantly decreased. No adverse events were reported.

Conclusion

The daily use of Cysticlean™ 240 mg was associated with a reduction of UTIs and a prolongation of UTI-free survival compared to placebo treatment, supporting its use as prophylaxis in this patient population.

Trial registration

Clinicaltrials.gov, identifier NCT03032003.

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Data availability

The data presented in this study are available within the article and are kept at the Department of Hygiene and Epidemiology of Larissa in Thessaly.

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Acknowledgements

Authors thank all clinical and laboratory staff involved and all participants of the study. Cysticlean™ 240mg was supplied by Stilvi Pharmaceuticals SA (Vita Green’s local representative in Greece).

Funding

The implementation of the doctoral thesis was co-financed by Greece and the European Union (European Social Fund-ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning» in the context of the Act “Enhancing Human Resources Research Potential by undertaking a Doctoral Research” Sub-action 2: IKY Scholarship Programme for PhD candidates in the Greek Universities.

Author information

Authors and Affiliations

  1. Department of Urology, School of Health Sciences, Faculty of Medicine, University of Thessaly, University Hospital of Larissa, 41110, Larissa, Greece

    Eleftherios Tsiakoulias & Vassilios Tzortzis

  2. Department of Urology, Medical School, University of Cyprus, Nicosia, Cyprus

    Stavros Gravas

  3. Laboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 41222, Larissa, Greece

    Christos Hadjichristodoulou, Maria Kyritsi, Katerina Dadouli, Alexia Matziri, Konstantina Kola & Evangelia Vacthsioli

  4. Intensive Care Unit, General Hospital of Larissa, 41221, Larissa, Thessaly, Greece

    Katerina G. Oikonomou

  5. Department of Occupational Therapy, Melathron Agoniston EOKA, 4549, Limassol, Cyprus

    Marianna Tsiakoulia

  6. Department of Immunology and Histocompatibility, Faculty of Medicine, University of Thessaly, 41500, Larissa, Greece

    Michaela Gianniou

Authors
  1. Eleftherios Tsiakoulias
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  2. Stavros Gravas
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  3. Christos Hadjichristodoulou
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  4. Katerina G. Oikonomou
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  5. Maria Kyritsi
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  6. Katerina Dadouli
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  7. Alexia Matziri
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  8. Konstantina Kola
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  9. Evangelia Vacthsioli
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  10. Marianna Tsiakoulia
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  11. Michaela Gianniou
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  12. Vassilios Tzortzis
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Contributions

Conceptualization—protocol development, V.T., S.G. H.C.; supervision, V.T.; writing—original draft preparation, Ε.Τ., V.T., P.J.V.; writing—review and editing E.T., V.T., O.K.G., S.G., H.C., M.T., M.K., K.D., M.G.; data collection, E.T.; data analysis, M.K., A.M., K.K., E.V., statistical analysis, K.D.; project administration, V.T., S.G., H.G., E.T., and K.G.O. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Eleftherios Tsiakoulias.

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Conflict of interest

The authors declare no conflict of interest.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki and its later amendments. The protocol, the consent form and all procedures of this trial were reviewed and approved by the institutional ethics committee of University General Hospital of Larissa (No 2017–5506/19–10-2017). Written informed consent was obtained from all study participants prior to randomization. This randomized clinical trial is registered at ClinicalTrials.gov, identifier: NCT03032003.

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All authors approved the final version of the manuscript for submission.

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Tsiakoulias, E., Gravas, S., Hadjichristodoulou, C. et al. Randomized, placebo-controlled, double-blinded study of prophylactic cranberries use in women with recurrent uncomplicated cystitis. World J Urol 42, 27 (2024). https://doi.org/10.1007/s00345-023-04741-0

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  • DOI: https://doi.org/10.1007/s00345-023-04741-0

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