Assess the Efficacy of OM-89 vs Placebo in Reducing Antibiotic Consumption Associated With the Treatment of Urinary Tract Infections in Patients With Neurogenic Bladder

Phase

Condition

Bladder Disorders

Urinary Incontinence

Enuresis

Treatment

OM-89 [Uro-Vaxom® Capsule]

OM-89 [Uro-Vaxom® Capsule] OM-89 placebo [Uro-Vaxom® Capsule placebo]

Clinical Study ID

NCT06588010

PIROTH OMPharma 2023

Ages > 18
All Genders

Study Summary

Recurrent urinary tract infections (UTIs) in patients with a neurogenic bladder using clean intermittent catheterization (CIC) are a major problem. In this population, urinary tract infections are the most frequent cause of morbidity and the second leading cause of mortality (Buzzell A, Spinal Cord, 2020). It is also the leading cause of healthcare use and consumption (A. Dinh, MMI 2019). In addition, multidrug-resistant bacteria (MRB) are frequently implicated, accounting for up to 50% of cases (Samal V BMC Infect Dis 2022, A. Dinh Spnal cord 2016), due to high exposure to antibiotics and frequent and prolonged hospitalisations.

The very frequent recurrence of urinary tract infections encourages exposure to antibiotics, so prevention is of vital importance. Prevention based on treatments other than antibiotics (non-antibiotic prophylaxis) is of the greatest interest, not only to prevent UTIs, but also to reduce exposure to antibiotics and the ecological pressure they exert. However, few strategies are available, and very few have been well evaluated in high-risk populations.

Bacterial lysates such as Escherichia Coli extract (OM-89), an immunoactive prophylaxis, are an original and innovative strategy that has been developed for the prevention of recurrent UTIs, and could constitute a therapeutic option in particularly at-risk populations.

In vivo studies have shown that OM-89 :

increases IgA levels in intestinal secretions and in the urine of mice (Bosh AV Immunopharmacol Immunotoxicol 1988; Baier W Arzneim Forsch Drug Res 1997),
stimulates the production of serum IgG and IgA recognising a number of bacteria isolated from patients with urinary tract infections and enterohaemorrhagic E. coli infections (Huber M, Int J immunopharmacol 2000),
stimulates the killing capacity of rabbit polymorphonuclear leukocytes against E. coli and S. aureus (Nauck M, Int J Exp Clin Chemother 1991),
protects against acute infection with E. coli or P. aeruginosa,
and inhibits inflammation associated with lipopolysaccharide-induced cystitis in mice (Lee SJ, World J Urol 2006).

Clinically, certain studies in patients with recurrent UTIs have shown a significant reduction in the number of urinary tract infections with OM-89 compared to placebo or an antibiotic (Bauer Eur Urol 2005; Naber KG Int J Antimicrob Agents 2009; Wade DT, Clin Rehabil 2020).

However, these promising results suffer from methodological limitations and need to be confirmed by a high-quality trial carried out on a sample appropriate to the research question and in a homogeneous patient population.

Patients with spinal cord injuries are a population at high risk of recurrent UTIs, and prevention is a major issue, given the incidence of MRBs in this population. It is therefore important in this high-risk population not only to rigorously evaluate the efficacy of OM-89 in reducing antibiotic consumption for UTIs, but also to assess its impact on bacterial resistance and on the microbiota (urinary and digestive). These patients could therefore see significant benefits: less frequent urinary tract infections and reduced antibiotic use. In addition, this population could serve as a model for other populations with or without neurological impairment suffering from recurrent UTIs

Eligibility Criteria

Inclusion

Inclusion Criteria:

Person who has given written consent
Patient aged 18 years or older
Patient with a stabilised neurogenic bladder following spinal cord injury thaht hasnot progressed for more than 2 years and who has undergone a urodynamic examinationin the last 2 years.
Patients using CIC (5 to 6 per day)
Patients who have received at least 6 courses of antibiotic treatment for UTIs inthe 12 months prior to screening (whether for curative or prophylactic reasons)
Patients with a negative urine culture between screening visit and randomisation ortreated with antibiotics for urinary decontamination prior to randomisation.

Exclusion

Exclusion Criteria:

Person who is not affiliated with the national health insurance system
Person subject to a measure of legal protection (guardianship, tutorship)
Person subject to a court order
Adults unable to express consent
Patients using a urinary drainage method other than CIC
Patients with urinary lithiasis at the time of inclusion (assessed by renal imagingin the previous year as part of routine management for patients with a history(s) oflithiasis or within 3 years for patients with no history)
Presence of an endo-urinary device (urinary prosthesis, ureteral stent)
Enterocystoplasty or irradiated bladder (past or present)
Known allergy or previous intolerance to the active substance or one of theexcipients of OM-89 or placebo
Patient requiring ongoing or short-term prolonged antibiotic therapy (e.g. infectedbedsore, etc.)
Patient treated with bacterial lysates (including OM-89) in the 6 months prior torandomisation
Unable or unwilling to stop prophylactic antibiotic therapy prior to randomisation
Patient with a known malignant tumour or neoplasia
Patient with an autoimmune disease
Patient treated with long-term or bolus corticosteroids, anti-CD20 andanti-rejection therapy in the 6 months prior to screening
Patient currently taking part in another study on an investigational device or drugrelated to urinary tract infections, or who has received another investigationaltreatment in the 30 days prior to screening.
Patient unable to collect information in a daily diary.
Patient unable to understand follow-up by telephone.
Patients planning to move to another residence in the year following randomisation
Non-menopausal women who are not surgically sterile (bilateral oophorectomy orhysterectomy) AND pregnant, breast-feeding who are declare that they are planning toconceive at inclusion, or not using effective* contraception.

Study Design