Hyaluronate for the Treatment and Prevention of Recurrent Urinary Tract Infection in Women Suffering Atrophic Vaginitis
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Reduced incidence of medically confirmed urinary tract infection
研究概览
简要总结
In post-menopausal women, the condition atrophic vaginitis results from the loss of oestrogen and is characterised by dyspareunia (pain during intercourse), vaginal dryness, and vaginal irritation. It is often diagnosed alongside recurrent urinary tract infections (rUTIs) and may increase susceptibility to rUTI. Topical vaginal oestrogen can be used to re-condition the vaginal epithelium and also reduces the incidence of rUTIs. However, patients often express concerns about using oestrogen, a hormonal treatment. Studies also report side-effects including vaginal bleeding, discharge, burning and itching that underpin significant (28%) drop-out rates. Hence, alternative non-hormonal, non-antibiotic based therapies that treat the vaginal atrophy, but also reduce the incidence of rUTI are needed.
Recurrent UTI in adult women is common. Bacteria from the gut can colonise the vulvar epithelia and then the bladder, causing uncomfortable urinary symptoms (cystitis). The lifetime risk of a UTI is around 40% in adult women which increases in post-menopausal women. Annually, UTI incidence is 3%. Of those affected, 5% will suffer rUTI, rising to 13% in the over 60 population. This equates to over 300,000 of the adult female UK population annually affected by rUTI. The most frequent treatment for rUTIs is low dose antibiotics, but this treatment causes the bacteria carried by such women to become antibiotic resistant, which exacerbates the clinical problem. The prevalence of antimicrobial multi-resistance within post-menopausal women suffering from rUTI is around 25% and was shown to rise to more than 80% following prolonged antibiotics. These data support the use of non-antibiotic treatment strategies that prevent rUTI and the emergence of drug resistant micro-organisms.
This study will compare two groups with differing treatment strategies. One group will be primarily treated for atrophic vaginitis with topical vaginal hyaluronate and the other will be primarily treated for their recurrent UTI with intravesical hyaluronate.
详细描述
Study purpose A potential alternative to prophylactic antibiotic treatment and topical vaginal estrogen treatments is the compound hyaluronate (HA). HA is already utilised in the UK to treat rUTIs, but is delivered as a bladder instillation (Ialuril®). A small meta-analysis of intravesical hyaluronate therapy incorporating four studies (two randomised, two non-randomised, 143 patients) investigating the use of this treatment in recurrent UTI, reported a statistically significant improvement in the rates of recurrent UTI (mean difference -3.4 episodes per patient year, 95% confidence interval -4.3 to -2.5). HA is also available as a vaginal cream, Hyalofemme®, which is used clinically to treat atrophic vaginitis. The evidence suggests that many women suffering vaginal atrophy also experience recurrent UTIs. However, the effect of HA treatment in reducing concomitant rUTIs in such patients has not been reported.
The need for this study is also supported by current guidance documents. The 2012 Scottish Intercollegiate Guideline Network (SIGN) guideline emphasises the need to avoid "unnecessary antibiotic prescribing," specifically highlighting the issue of antibiotic-resistant [E. coli] UTI. Additionally, the UK antimicrobial resistance strategy documents antibiotic resistance as a key concern and as such, lends support to the investigation, and use of alternative antimicrobial therapies. The use of non-antibiotic preventative treatments for rUTI has also been accentuated by current UK, European and USA guidelines to minimise antibiotic resistance. Therefore, this pilot study investigating the efficacy of a treatment already prescribed for vaginal atrophy in reducing concomitant rUTI is not only addressing current directives, but will help inform whether topical HA therapy can be extended to all rUTI sufferers, thus helping to reduce global antibiotic use.
Evidence supporting the effectiveness of hyaluronate (HA) in treating rUTI is available, but at present the therapy is administered directly to the bladder, which involves catheterisation, managed through hospital visits. In contrast a HA topical treatment can be patient managed at home. If from the data collated the topical HA therapy shows a comparable efficacy in reducing rUTI, then these data will underpin a large-scale clinical trial examining the use of this non-hormonal, non-antibiotic based agent for the treatment and prevention of rUTI in patients.
While the focus of this initial study is on post-menopausal women suffering vaginal atrophy and rUTI, it is also anticipated that this treatment could be broadened to all women suffering rUTIs. One particular target group are females carrying the TLR5392Stop polymorphism who are at increased risk of rUTI, thus signalling an era of personalised medicine for an infection related disease. It is also envisaged that topical HA therapy could be prescribed as a urethral barrier cream for men suffering uncomplicated rUTI.
Study design This study was designed through a collaboration of clinical urologists and basic scientists with an interest in the concomitance of atrophic vaginitis and recurrent UTI. The proposal was peer-reviewed before funding was granted by The Urology Foundation. This single-centre study is located at the Urology Department, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, NE7 7DN. Participants recruited will be post-menopausal women identified as either having gone through the menopause naturally or having had an oophorectomy, and not on hormone replacement therapy (HRT) in the last two years, and who suffer from vaginal atrophy and rUTI. Patients will have either 3 confirmed episodes of UTI in the preceding year or 2 episodes in the last 6 months. Patients will exhibit the symptoms and signs of atrophic vaginitis, which will be diagnosed by their responsible clinician. The study duration is 24 months, with a patient recruitment period of 12 months. Patient follow up and laboratory work will proceed until the end of month 23, with data analyses and final report preparation in the final month.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 90 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •• Postmenopausal women not receiving hormonal supplementation.
- •Women with atrophic vaginitis and rUTI who, in consultation with a clinician, have decided that either hyaluronate treatment (intravesical or vaginal) is an appropriate option.
- •Women who have suffered at least three episodes of symptomatic UTI within the preceding 12 months or two episodes in the last 6 months.
- •Able to attend a urology clinic for catheterisation on a regular basis (initially weekly) to initiate intravesical bladder instillation treatment.
- •Able to apply vaginal hyaluronate gel at home every 3 days.
- •Able to give informed consent for participation in study.
- •Able and willing to adhere to a 9-month study period.
排除标准
- •• Postmenopausal women receiving hormonal supplementation (e.g. HRT or oestrogen creams).
- •Women unable to use hyaluronate e.g. due to previous sensitivity issues.
- •Women with urinary tract abnormalities that are considered to be contributory to the occurrence of rUTI.
- •Presence of symptomatic UTI - this will be treated and symptoms resolved prior to randomisation.
- •Women currently using hyaluronate for either treatment of atrophic vaginitis or prevention of recurrent UTI or women who have used either study treatment in the preceding 12 months.
- •Women receiving prophylactic antibiotics.
- •Catheter usage.
研究组 & 干预措施
Hyalofemme
Hyalofemme is a cream/gel containing hyaluronic acid, designed to be applied vaginally. This is primarily used in treatment of atrophic vaginitis and is applied by the patient once every three days. We intend treatment to continue for 6 months.
干预措施: Hyalofemme (Device)
Ialuril
Ialuril is a bladder instillation designed to be delivered to the bladder via catheter. This is primarily used in patients suffering from recurrent UTI and acts to help rebuild the lining of the bladder, reducing irritation. Ialuril is applied weekly for 6 weeks, followed by every 2 weeks for 6 weeks, then once monthly for maintenance. Treatment will be continued for 6 months.
干预措施: Ialuril (Device)
结局指标
主要结局
Reduced incidence of medically confirmed urinary tract infection
时间窗: Number of UTIs will be assessed at both 6 months (end of treatment) and 9 months (end of follow-up period)
Occurrence of symptomatic UTI with prescription and taking of a treatment course of antibiotics for UTI. Applicable for both treatment arms in comparison to baseline established in the previous 12 months.
次要结局
- Number of microbiologically-proven UTIs(6 and 9 months)
- Effect on vaginal atrophy(3, 6 and 9 months)
- Uropathogen identification(9 months)
- Innate immune response in urine and vaginal douche samples measured by ELISA for cytokines and antimicrobial peptides (e.g. interleukin-8, beta-defensin 2).(9 months)
- Analysis of polymorphisms in receptor proteins known to be involved in UTI(9 months)
- Participant quality of life - does either treatment increase overall quality of life by decreasing symptoms from UTI and/or atrophy?(3, 6 and 9 months)
- Reduction in antibiotic use for UTI as a result of hyaluronate treatment by either route of administration(Results will be analysed at both end of treatment (6 months) and end of follow-up (9 months))