Clinical trial NCT06815120: A Novel Ureteric Stent in Kidney Stone Patients and Oncology Patients Compared to a Conventional JJ Stent
Official title: Two Single Arm, Multicentre Unblinded First-in-human Trials Investigating a Novel Ureteric Stent to Determine the Reduction of Encrustation, Biofilm Deposition and Complications Compared to a Conventional JJ Stent
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Catheter Blockage
Oncology
Kidney Stone
Lead sponsor: University of Southampton
Sponsor class: OTHER
Collaborators: name: University Hospital Southampton NHS Foundation Trust
name: National Institute for Health Research, United Kingdom
name: University College London Hospitals
First posted: 2025-02-07
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Two single arm, multicentre unblinded first-in-human trials, including 2 phases and a qualitative substudy
Primary purpose: TREATMENT

Brief summary: Urological stents and catheters often lead to inflammation, causing pain and infection in the urinary tract. Moreover, 80% of stents are associated with pain, negatively impacting on QoL and mental health. Offering novel designs with significantly lower E\&B leads to a reduction in UTIs and improves QoL. Reducing hospital admissions (from 3 to 1 per patient, annually) would free \>100,000 bed-nights, allowing the elderly to regain independence. Our proposed research could have a significant impact towards fulfilling the 'healthy-ageing' Grand Challenge. Additionally, the novel stent reduces prevalence of infections and therefore, of antibiotic prescriptions contributing to the Global AMR challenge.

Detailed description: Ureteric stents and catheters are deployed clinically as temporary measures to restore urinary drainage, in patients with kidney stones, tumours and strictures. Prevalence of these increases with age. Device-associated encrustation-and-biofilm-formation (E\&B) are key complications, leading to urinary-tract-infections (UTIs) in \>90% of stents, causing stent blockage and favouring development of antibiotic resistance.

UTIs are a significant cause of morbidity, especially among the elderly population, with 4,835 deaths in England and Wales reported in 2012. The National Institute for Health Research reported that 1-3% of all primary care consultations concern UTI-related symptoms, leading to 13.7% of antibiotic prescriptions globally. The report also revealed that \>92m people globally are diagnosed with UTIs annually.

Urological-device-associated infections significantly compromise patient' quality of life and the effectiveness of services, imposing a £2.5b annual burden on the NHS. Patients' exposure to hospital environment and general anaesthetic use impact on Quality-of-Life (QoL), resulting in unnecessary hospital bed-nights. We have developed a novel urological stent associated with significantly reduced particle deposition , potentially extending the stent's lifetime, resulting in reduced hospitalisation and improved QoL.

Urological stents and catheters often lead to inflammation, causing pain and infection in the urinary tract. Moreover, 80% of stents are associated with pain, negatively impacting on QoL and mental health. Offering novel designs with significantly lower E\&B leads to a reduction in UTIs and improves QoL. Reducing hospital admissions (from 3 to 1 per patient, annually) would free \>100,000 bed-nights, allowing the elderly to regain independence. Our proposed research could have a significant impact towards fulfilling the 'healthy-ageing' Grand Challenge. Additionally, the novel stent reduces prevalence of infections and therefore, of antibiotic prescriptions contributing to the Global AMR challenge.

Considering only onco-urological patients, \>30,000 stents are inserted every year across 200 NHS units. Due to stent failures, each patient undergoes 3 to 6 replacements, resulting in \>90,000 stent replacements. Under the current tariff-based system, hospitals are paid for each intervention, costing the NHS \>£3,500, bringing the total cost of replacements to \~£315m annually. Unnecessary replacements increase the number of bed-nights and use of anaesthetics. A longer-lasting stent means that each patient comes to the hospital ideally only once, reducing their exposure to the hospital environment and anaesthetic-associated risks. Additionally, under the current model hospitals would improve their quality of service and save at least 2 bed-nights per patient. The NHS is moving towards a "block contract" model, meaning that hospitals will receive a lump sum for the year and they'll regularly monitor budgets and improve cost efficiency where possible. Improved stents will allow the same urology budget to deliver more healthcare, reducing theatre time for stent insertion-and-replacement. Our innovative stent design offers a potential annual saving of \>£210m for the NHS, allowing hospitals to reallocate their resources. Today E\&B is still a major determinant of stent failure and associated side effects. We aim to address this challenge through our novel stent, and if equivalent safety and improved efficacy are demonstrated, anticipate market launch via third-party suppliers 2-3 years post project.

Solutions to break this pathway (stent presence \>\> inflammation, pain and infection) have been developed, including materials (e.g. metallic alloys, polymers, biodegradable and drug-eluting materials), coatings (e.g. heparin, chitosan, hydrogel, carbon) and shapes (e.g. double-J, loop, mesh, string, expandable) to improve the efficacy and safety of stents. Despite all these advances, there is still a significant prevalence of E\&B. This is also due to the lack of studies correlating fluid dynamic metrics with deposition of particles causing E\&B. The lead applicant's PhD investigated the mechanisms of particle deposition in urological stents, and successfully determined fluid dynamic parameters governing particle deposition on ureteric stents and catheters. His research led to developing a stent with specially shaped side-holes that prevent stagnation points (i.e., areas of low flow that cause particles to settle and E\&B). These developments demonstrated \>80% reduction in particle deposition at side-holes, in-vitro. Their innovative architecture can be implemented on stents and catheters. The technology, including the stent design and manufacturing process, is protectable - Patent# WO2019048860A1, WIPO(PCT). These results were further validated in an animal study (6 pigs: 3 novel-design-stent vs 3 conventional-design-stent for a 4-weeks period) at Stone-Centre at Vancouver-General-Hospital (VGH), a centre of excellence in animal studies on urological products. The study (available upon request) concluded that the functionality of stents with novel side-holes is the same as that of standard stents in terms of safety. Specifically, the novel stent does not result in increased risk of irritation, inflammation and hydronephrosis. Furthermore, SEM/EDX imaging showed that the novel design decreased the build-up of particles on the stent surface. Thus, it demonstrated significant potential for the new side-hole configuration to change patterns of particle deposition on the stent's surface, decreasing encrustation

Eligibility criteria: Inclusion Criteria:

1. Aged 18 years or over
2. Ureteric stents clinically indicated either due to kidney stones or abdominal/pelvic cancers compressing ureters
3. Previous experience with ureteric stents
4. Awaiting insersion/replacement of stents
5. Ability to give consent
6. Ability to interact with study documentation
7. Sufficient English to complete study documentations and questionnaires

Exclusion Criteria:

1. Expected survival \<4months
2. Unfit for stent insertion
3. Unable to comply with study processes Pregnancy

Primary outcomes:
measure: To determine rates of stent failure
timeFrame: From enrolment to stent removal (4 weeks for Kidney cohort), (25 weeks for Oncology cohort)
Secondary outcomes:
measure: To assess extent of encrustation and biofilm (E&B)
timeFrame: From enrolment to stent removal (4 weeks for Kidney cohort), (25 weeks for Oncology cohort)
measure: To determine whether the novel stent leads to better clinical outcomes
timeFrame: From enrolment to completion of patient questionnaires 2-3 weeks post surgery 2 (4 weeks for Kidney cohort), 2-3 weeks post surgery 2 (~25 weeks for Oncology cohort)
measure: To assess impact of the novel stent on quality of life
timeFrame: Within first month of stent removal for participants (4 weeks for Kidney cohort), (25 weeks for Oncology cohort)
measure: To understand patient experience in having the novel ureteric stent inserted and reason for participation in the trial
timeFrame: From enrolment to stent removal (4 weeks for Kidney cohort), (25 weeks for Oncology cohort)
Other outcomes:
measure: To assess extent of encrustation and biofilm (E&B)
timeFrame: After surgery 2 for Kidney Stone cohort (4 weeks) and surgery 2 for Oncology patients (25 weeks)
Locations:
Study officials:
affiliation: University of Southampton
name: Ali Mosayyebi
role: PRINCIPAL_INVESTIGATOR
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