Preventing UTIs in Chronic Neurogenic Bladder Dysfunction (Mix Methods)
Condition: UTI; Neurogenic Bladder; Antibiotic Resistance
MeSH terms: Urinary Tract Infections; Urinary Bladder, Neurogenic
Study type: Interventional
Phase: Phase 2

Summary: 
      Due to the damage caused to the spinal cord, patients with spinal cord injury, cauda equina
      syndrome, multiple sclerosis and transverse myelitis may encounter loss of bladder function,
      which in turn can lead to a debilitating and costly complication: Urinary Tract Infections
      (UTIs). Given that these patients with loss of bladder function do not normally feel symptoms
      like pain - as would be the case in otherwise healthy persons - there is no clear agreement
      among experts on which signs and symptoms are indicative of a UTI. Although strong evidence
      is lacking, antibiotics have been widely used for prevention of recurrent UTIs in patients
      with loss of bladder function. However, this approach is now being questioned as antibiotic
      resistance has become a world-wide health concern. Policy makers recently stressed the
      importance of research into alternative preventative treatments. The use of immunotherapy is
      one such an alternative approach, which works by stimulating the body's immune system. One of
      these immunotherapy is a Uro-Vaxom® oral capsule which consists of inactivated traces of the
      bacteria that normally cause at least 83% of UTIs in patients with loss of bladder function.
      Previous studies show that Uro-Vaxom® resulted in a significant reduction of UTIs in
      otherwise healthy patients, as well as being safe to use. Before investigating the effects of
      this promising new immunotherapy, this proposed study aims to clarify two crucial issues.
      First, after reviewing the literature and appraising patients', carers' and healthcare
      professionals' experiences, the aim is to reach an agreement on how to measure a symptomatic
      UTI in patients with loss of bladder function that results from a spinal cord lesion. Second,
      using Uro-Vaxom® Investigators aim to conduct a smallscale, placebo-controlled trial with 48
      participants to investigate the feasibility of carrying out a larger trial on prevention of
      symptomatic UTI in such patients.
    

Detailed description: 
      Each year in the UK 1,200 people sustain a spinal cord injury, 600 people will be diagnosed
      with cauda equina syndrome, 6,000 with multiple sclerosis and 300 with transverse myelitis.
      These four patient groups all suffer from neurological disorders of the spinal cord,
      resulting in loss of normal bladder function known as neurogenic bladder dysfunction. This in
      turn can lead to urinary tract infections (UTIs). UTIs are a commonly recurring and
      debilitating complication, with spinal patients experiencing 2.5 episodes per patient per
      year on average. This not only results in 16% of hospital readmissions and costs of care of
      up to £125 million spent by the NHS on treating UTIs every year, but also has a dramatic
      impact on patients' quality of life.

      A recent NICE guideline highlighted the methodological difficulties of research into the
      prevention of UTIs in patients with neurogenic bladder dysfunction. Given that this group of
      patients normally do not feel symptoms like 'pain' and 'a frequent urge to urinate', it can
      be difficult to distinguish between bladder colonisation (asymptomatic bacteriuria) and true
      infection (a symptomatic UTI). To date, there is no clear agreement among experts on which
      signs and symptoms are indicative of a symptomatic UTI. Although strong evidence is lacking,
      antibiotics have been widely used for the prevention of recurrent UTIs in patients with
      neurogenic bladder dysfunction. However, this approach is now being called into question as
      antibiotic resistance has become a world-wide health concern.

      In the recently published 'UK Five Year Antimicrobial Resistance Strategy', policy makers
      stressed the importance of research into alternative preventative treatments. Immunotherapy
      potentially offers such a (cost-) effective alternative to antibiotic therapy for UTI
      management. At least 83% of community-acquired complicated UTIs are caused by Escherichia
      coli (E. coli). Uro-Vaxom® (OM-Pharma, Switzerland) is an orally administered, bacterial
      vaccine which consists of a 6mg lyophilised (heat-inactivated) mix of E. coli membrane
      glycoproteins.

      Previous studies showed that Uro-Vaxom® resulted in a significant reduction of UTIs in
      otherwise healthy women with recurrent cystitis, as well as being safe to use.

      Before investigating the effects of this promising new vaccine in patients with neurogenic
      bladder dysfunction, two crucial issues will need to be clarified. First, consensus must be
      reached on how to measure a symptomatic UTI in this group of patients. Second, the
      feasibility of carrying out a larger, definitive randomised controlled trial on the
      prevention of symptomatic UTI in patients with neurogenic bladder dysfunction must be
      established. The central aim of the proposed mixed method study is to clarify these two key
      methodological and feasibility issues.

      In the first stage of this study is to carry out qualitative interviews to explore patient
      experiences and views of symptoms and signs associated with a UTI. These results, combined
      with findings from a literature review, will enable the design of a quantitative patient
      survey which will be distributed by four service user organisations to people with neurogenic
      bladder dysfunction. Finally, taking the results from all preceding stages, a final
      definition, or algorithm, will be discussed before and during a consensus meeting.

      In the second stage of this study, a small-scale parallel, double-blinded, randomised,
      placebo-controlled, multicentre trial will be conducted to investigate the feasibility of
      carrying out a larger well-powered study on the prevention of symptomatic UTI in patients
      with neurogenic bladder dysfunction. Forty-eight patients will be randomly assigned treatment
      with Uro-Vaxom®, or placebo, for 3 months and followed-up for a further 3 months.

      This is to expose any pitfalls or areas requiring re-designing, such as logistics,
      recruitment and compliance rates, in order to refine the protocol of a definitive clinical
      trial.
    

Intervention name(s): Uro vaxom; Placebo comparator
Intervention type(s): Drug; Other
Intervention description(s): Prevention of recurrent symptomatic lower urinary tract infections; Placebo comparator
Other intervention name(s): OM-89; Placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Spinal Cord Injuries; Multiple Sclerosis; Transverse Myelitis; Neurogenic Bladder Dysfunction; Feasibility Study; Urinary Tract Infection