Hyaluronate for the Treatment and Prevention of Recurrent Urinary Tract Infection in Women Suffering Atrophic Vaginitis

NCT03981458 | Unknown

• 2 other identifiers: HATPIN8904
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Atrophic Vaginitis; Urinary Tract Infections

Outcome Measures

Primary Outcomes (1)

• Reduced incidence of medically confirmed urinary tract infection

  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.

  Number of UTIs will be assessed at both 6 months (end of treatment) and 9 months (end of follow-up period)

Secondary Outcomes (7)

• 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

Study Arms (2)

Hyalofemme

ACTIVE COMPARATOR

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.

Device: Hyalofemme

Ialuril

ACTIVE COMPARATOR

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.

Device: Ialuril

Interventions

Hyalofemme DEVICE

Gel made with hyaluronic acid to be applied vaginally to treat atrophic vaginitis.

Also known as: Hyaluronic acid gel, Hyaluronate gel

Hyalofemme

Ialuril DEVICE

Bladder instillation of hyaluronic acid to treat recurrent UTI.

Also known as: Hyaluronic acid instillation, Hyaluronate instillation

Ialuril

Eligibility Criteria

• Age: 30 Years - 90 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Newcastle-upon-Tyne Hospitals NHS Trust: lead
• The Urology Foundation, UK: collaborator

Study Sites (1)

Freeman Hospital

Newcastle upon Tyne, Tyne and Wear, NE7 7DN, United Kingdom

RECRUITING

MeSH Terms

Conditions

Atrophic Vaginitis; Urinary Tract Infections

Condition Hierarchy (Ancestors)

Vaginitis; Vaginal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infections; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Christopher Harding, MD

  Newcastle-upon-Tyne Hospitals NHS Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christopher Harding, MD

CONTACT

0191 2337321; chris.harding@nuth.nhs.uk

Judith Hall, PhD

CONTACT

0191 2088346; judith.hall@ncl.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Atrophic vaginitis and recurrent urinary tract infection are often found concurrently in post-menopausal women. The argument over which condition appeared first, or if one is caused by the other, is prevalent in clinical settings and there is no official guidance as to which should be treated first. We propose two arms to this study - one treating the atrophic vaginitis via use of Hyalofemme cream (hyaluronate cream), and the other treating recurrent UTI by use of Ialuril (hyaluronate bladder instillation). We intend to investigate the effect on the incidence of UTI in the patients with both treatments, as well as focusing on some markers of the immune response in the urine and vaginal douche samples from these participants.

Study Record Dates

• First Submitted: January 29, 2019
• First Posted: June 10, 2019
• Study Start: July 1, 2019
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2020
• Last Updated: July 8, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)