Clinical trial NCT02591901: Preventing UTIs in Chronic Neurogenic Bladder Dysfunction (Mix Methods)
Official title: Prevention of Recurrent Symptomatic Urinary Tract Infections in Participants With Chronic Neurogenic Bladder Dysfunction: A Mixed Method Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: UTI
Neurogenic Bladder
Antibiotic Resistance
Keywords: Spinal Cord Injuries
Multiple Sclerosis
Transverse Myelitis
Neurogenic Bladder Dysfunction
Feasibility Study
Urinary Tract Infection
Lead sponsor: Buckinghamshire Healthcare NHS Trust
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
name: Oxford Clinical Trials Research Unit
First posted: 2015-10-30
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Have a clinical diagnosis of spinal cord injury, multiple sclerosis, transverse myelitis or cauda equina damage;
* Have had the diagnosis of the spinal pathology for at least 12 months;
* Have not had any significant changes in the underlying condition for 12 weeks
* Be living in the community (not in residential care)
* Aged 18 to 75 years
* Have had at least three urinary tract infection episodes treated using anti-biotics over the preceding 12 months;
* If a woman of child-bearing age, is willing to use contraception for the duration of the study
* Having the mental capacity to give informed consent

Exclusion Criteria:

* Have had surgical alterations to the bladder, excluding supra-pubic catherisation.
* Known hypersensitivity to the active principle or to any of the excipients of Uro-Vaxom®
* Being unwilling to take a product containing gelatin (e.g. vegetarians)

  * recruitment can be postponed until antibiotics have not been used for a period of 14 days and symptoms of a UTI have subsided

Primary outcomes:
measure: Checklist or consensus guideline which can be used to measure a symptomatic urinary tract infection and Practicality of carrying out a definitive randomised controlled clinical study
timeFrame: 23 months
Secondary outcomes:
measure: Number of participants willing to participate
timeFrame: 14 months
measure: Number of successfully collected urine samples via courier
timeFrame: 14 months
measure: Drug compliance
timeFrame: 14 months
Other outcomes:
Locations:
city: Aylesbury
country: United Kingdom
facility: Stoke Mandeville Hospital
state: Buckinghamshire
city: Oxford
country: United Kingdom
facility: Oxford Centre for Enablement
state: Oxfordshire
Study officials:
affiliation: Stoke Mandeville Hospital
name: Maurizio Belci, DMS MSc MRCS FRCP
role: PRINCIPAL_INVESTIGATOR
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