A double-blind, randomized, placebo-controlled, multicenter clinical trial of the efficacy and safety of oral enzyme combination in the complex treatment of patients with exacerbation of chronic recurrent uncomplicated cystitis

Kupriyanov Yu.A., Zaitsev A.V., Bernikov A.N., Khodyreva L.A., Pushkar D.Yu.

1) Federal State Budgetary Institution of Higher Education «Russian University of Medicine» of the Ministry of Health of the Russian Federation, Moscow, Russia; 2) State Budgetary Institution «Scientific Research Institute of Health Organization and Medical Management» of the Department of Health of the City of Moscow, Moscow, Russia; 3) «Moscow Urological Center» State Budgetary Healthcare Institution «Botkin City Clinical Hospital» of the Moscow City Department of Health, Moscow, Russia

The treatment of recurrent lower urinary tract infections (RLUTIs) remains unresolved due to increasing antibiotic resistance and the ability of pathogens to form biofilms and parasitize intracellularly, creating microbial communities with biofilm-like properties. Therefore, great importance is placed on studying the effect of combination therapy on recurrent inflammation in the bladder mucosa using alternative enzymatic preparations, such as Wobenzym®. This preparation exhibits anti-inflammatory, immunomodulatory, fibrinolytic, antiplatelet, and anti-edematous effects, as confirmed by several studies. Based on the above, we have planned and conducted a clinical trial in a group of patients with recurrent lower urinary tract infections. Study objective: To evaluate the efficacy and safety of Wobenzym® compared to placebo as part of combination therapy in patients with exacerbation of chronic recurrent uncomplicated cystitis. Materials and methods: The clinical part of the study was conducted in compliance with all GCP requirements, in 20 research centers in the Russian Federation. The study included screening, therapy period and follow-up period – 8 planned visits and unplanned in case of disease relapse. 640 patients were included in the study, 638 patients took the study drug and were randomized into two groups: Wobenzym Group – 320 and Placebo Group – 318 women. As an antibacterial therapy, all patients were prescribed fosfomycin trometamol (Monural®). Group I of patients additionally received Wobenzym®, Group II – Placebo. Comparative analysis did not reveal statistically significant differences between the groups in somatic status and lifestyle, as well as its characteristics (p>0.05). In accordance with the primary endpoint, the incidence of recurrent exacerbation of chronic recurrent uncomplicated cystitis was assessed in the groups. Secondary efficacy criteria included a comparative assessment of the dynamics of changes in the main clinical symptoms; the proportion of patients who reported the absence of pain at the completion visit according to the pelvic pain, urgency, and frequency of urination symptom scale; the proportion of patients with symptoms of a current exacerbation of the disease after 14, 28, 56, and 84 days of therapy according to the patient diary; the dynamics of changes in objective laboratory parameters; the frequency of dysbiosis before and after therapy. The safety of Wobenzym® was also assessed. Results. In the Wobenzym group, recurrent exacerbation of chronic recurrent uncomplicated cystitis was observed in 12.62% of patients (95% CI: 8.94; 16.29), in the Placebo group - in 24.53% of patients (95% CI: 19.77; 29.28) (p<0.05). The main symptoms of cystitis resolved statistically faster in patients receiving Wobenzym® (p<0.05). Laboratory safety parameters were comparable between groups. Wobenzym® therapy was accompanied by lower concentrations of proinflammatory and regulatory cytokines, particularly IL-8 and IL-10, with a clear trend toward increased efficacy in the late stages of observation. In this study, 191 AEs were recorded (86 in the Wobenzym Group and 105 in the Placebo Group). Discussion. Our results confirm previous studies and the stated pharmacological properties of Wobenzym. Conclusion. Wobenzym® is a safe and effective combination therapy for lower urinary tract infections, exhibiting anti-inflammatory and immunomodulatory effects to significantly reduce the recurrence of bladder mucosal inflammation.

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About the Authors

Corresponding author: L.A. Khodyreva – Doctor of Medical Sciences, Head of the Organizational and Methodological Department of Urology of the Moscow City Health Department State Budgetary Institution «Scientific Research Institute of Health Organization and Medical Management» of the Moscow City Health Department, Moscow, Russia; е-mail: khodyreva60@mail.ru

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