Title: Can novel ureteric stents offer a better patient outcome compared to existing standard ureteric stents (CASSETTE)
Funder: Department of Health and Social Care

Abstract: Research Question: Does a novel ureteric stent design, used as a direct substitute for existing devices, lead to reduced encrustation compared to a conventional stent? Background: Since 2015, our team has investigated the mechanisms behind stent Encrustation-and-Biofilm-Formation (E&B), leading to early removal/replacement. We identified key fluid metrics governing E&B, allowing us to introduce a specialised stent design that increases the force over area on the stent surface leading to a cleaner surface. This was demonstrated in computational-fluid-dynamic (CFD) models and validated experimentally. Then, a prototype was developed and successfully tested in pre-clinical models. In the context of the IDEAL-D [1] variant for medical devices, we have completed stage-0 and demonstrated: Safety in pigs. Reduction in E&B. We believe the device is ready for First-in-Human testing, thus are moving to IDEAL stage-1 to gather evidence for obtaining a CE/UKCA-mark through a notified body. Aims and Objectives: Product development and regulatory approvals. Completing pilot manufacturing. Completing Technical-Documentation to the MDR2017/745. Obtaining MHRA No Objection approval for human trial. Validating the controlled manufacture and sterilisation process (including selection of suitable packaging materials) conforming to ISO13485:2016. Installing ISO13485:2016 into Sooba-Medical. Developing design dossier for review by a Notified-Body as part of CE/UKCA-mark application process. IP development. The priority patent for this technology (&ldquo;Stent with Streamlined Side Holes&rdquo;), which includes the stent design and manufacturing process, was filed in 2017 in the UK by the University-of-Southampton (UoS). This was followed by a PCT-International application (WO2019/048860) that was submitted in 2018. Currently, there are patent applications pending in the US and Europe. Market assessment, business case and commercial strategy. A detailed market assessment will include the choice of region, market size, timeline, cost comparison to competition, price strategy, market penetration. Establishing Sooba-Medical as the commercial vehicle. IP position and relationship with UoS. Determine cost of manufacturing, sales, and marketing. Preliminary health economic assessment, involving Wessex AHSN. Milestones and deliverables: Year 1: Finalised, sterilised and packaged prototype for testing MHRA No objection letter in place Patent landscape mapped STOP/GO MILESTONE &ndash; MHRA approval, trial protocol and the appropriate ethics in place? Year 2: Recruiting trial candidates at two NHS trusts UHS &ndash; stone patients UCLH &ndash; cancer patients Market assessment: business plan, applicability STOP/GO MILESTONE &ndash; sufficient recruitments are in place? A robust business plan developed? UHS trial started? Year 3: Finishing UHS and UCLH trials Installing ISO13485:2016 into Sooba-Medical Application for UKCA/CE-mark FINAL MILESTONE &ndash; have a safe, clinically acceptable, and commercially viable product ready for analysis and development of wider trials, including demonstration of proof-of-concept to support a future proposal for an EME-funded efficacy study. Anticipated Impact and Dissemination: Findings will inform final development of the product, manufacturing scale-up, submission for regulatory approval, early marketing, and design of larger studies to demonstrate impact for patients and the NHS. Dissemination of findings will be through academic routes via a protocol paper, main clinical results paper and an economic paper. Participants will also receive the study results.

Lay abstract: Background The urinary system is complex and difficult to repair. Many factors can affect urine drainage, resulting in inability to urinate, pain, and kidney damage. Stents and catheters are tubular devices that are used as temporary solutions to maintain urine drainage while exploring patient-specific long-term treatments. These devices are prone to blockage due to the build-up of crystals and bacterial deposits (encrustation-and-biofilm-formation (E&B)), causing infection. Infections associated with stents and catheters impose a &pound;2.5b annual burden on the NHS; they require antibiotics and possibly surgery under general anaesthetic, with negative effects on patients health and increased demand on clinical services. Aims We have identified a reason behind failure of these devices and have developed new patented stents preventing blockage by crystals and bacterial build-up. To date, we have conducted laboratory experiments and animal testing, and aim to perform human trials to assess whether they: Reduce encrustation and biofilm formation Increase stent lifetime Reduce premature removal Reduce unplanned operations Reduce pain Improve quality of life Reduce infection Design and methods used To test these new stents, we will run 'First-in-Human' trials to assess safety, performance, and patient acceptability, providing data for analysis and development of wider clinical trials. We have identified two clinical subgroups where this device may offer advantages against E&B: Short-term: Patients with kidney/renal stones who require stent insertion ( Long-term: Patients with abdominal/pelvic cancers compressing the ureters (16 weeks indwelling time). We expect the device to have similar performance and safety in both groups. If it underperforms in either group, it is likely to be the cancer group, due to disease characteristics. We therefore plan to assess the use of the device in both groups separately, and will only proceed to assessment in the cancer group if there are no safety concerns identified in the stone group. Patient and public involvement (PPI) A PPI officer and PPI members (with lived patient experience) are part of the core team and have helped developing this submission. Their involvement will include (but is not limited to): The PPI officer will help organise and deliver meetings with PPI members to advise on the design of forms and information for study participants, and will provide liaison between the project team and patients. PPI members will join meetings to contribute towards product development, design of Patient-Information-Sheet and Informed-Consent-Form (PIS-ICF), and development of the clinical trial protocol. Dissemination We will disseminate clinical protocols and findings through scientific publications and share findings with the public. The project outcome will inform final product development, manufacturing scale-up, submission for regulatory approval, early marketing, and design of larger studies to demonstrate impact for patients and the NHS.

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: RENAL AND UROGENITAL