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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 3
Recruiting
Conditions
Neurogenic Bladder
Interventions
Drug: OM-89 [Uro-Vaxom® Capsule] OM-89 placebo [Uro-Vaxom® Capsule placebo]
Drug: OM-89 [Uro-Vaxom® Capsule]
Registration Number
NCT06588010
Lead Sponsor
Centre Hospitalier Universitaire Dijon
Brief 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

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
110
Inclusion Criteria
  • Person who has given written consent
  • Patient aged 18 years or older
  • Patient with a stabilised neurogenic bladder following spinal cord injury for more than 2 years and who has undergone a urodynamic examination in 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 in the 12 months prior to screening (whether for curative or prophylactic reasons)
  • Patients with a negative urine culture at the screening visit or treated with antibiotics for urinary decontamination prior to randomisation.
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 ultrasound / scanner in the previous year as part of routine management)
  • 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 the excipients of OM-89 or placebo
  • Patient treated with bacterial lysates (including OM-89) in the 6 months prior to randomisation
  • 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 and anti-rejection therapy in the 6 months prior to screening
  • Patient currently taking part in another study on an investigational device or drug, or who has received another investigational treatment 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 or hysterectomy) AND pregnant, breast-feeding who are declare that they are planning to conceive at inclusion, or not using effective* contraception.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Patients in the experimental armOM-89 [Uro-Vaxom® Capsule] OM-89 placebo [Uro-Vaxom® Capsule placebo]-
Patients in the control armOM-89 [Uro-Vaxom® Capsule]-
Primary Outcome Measures
NameTimeMethod
Number of antibiotic treatment episodes for UTIs per person-days at risk during the first year.12 months

An episode of treatment is defined as a single prescription of a given antibiotic, regardless of its intended duration (curative or prophylactic). A day at risk is defined as a follow-up day without antibiotic treatment.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

CHU Dijon Bourgogne

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Dijon, France

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