Title: Proper Understanding of Recurrent Stress Urinary Incontinence Treatment in women (PURSUIT): A Randomised Controlled Trial of Endoscopic and Surgical Treatment
Funder: Department of Health and Social Care

Abstract: BACKGROUND AND STUDY AIMS_x000D_ Urinary leakage with physical activity is called stress urinary incontinence (SUI), and it affects about a quarter of women after pregnancy. Until recently, the most common treatment was a surgical operation which helps to support the tube which takes urine from the bladder to the outside (urethra) called midurethral (mesh) tape (MUT). Currently, there are strict rules in the NHS regulating the use of mesh and this study will adhere to those rules. _x000D_ _x000D_ Unfortunately, symptoms can come back after treatment, this is called recurrent SUI. In some cases, symptoms may never have gone away, this is called persistent SUI._x000D_ _x000D_ Treatment options for recurrent or persistent SUI are:_x000D_ 1. Injections into the urethra to help it to seal when leaks might happen called Endoscopic bulking injections. The injections are done using a cystoscope to inspect the inside of the bladder and urethra._x000D_ 2. Surgical operations:_x000D_ - A strip of the patient’s own tissue (taken from the tummy area) is used to support the urethra (autologous fascial sling). _x000D_ - Stitches are used to lift the vagina so that it supports the urethra (colposuspension). _x000D_ - An implant device is placed around the urethra to gently squeeze it and prevent leaking (artificial urinary sphincter). _x000D_ - A medical mesh tape is placed in the vagina to support the urethra (midurethral tape). Note: NHS rules restrict the use of mesh for vaginal surgery. At the time of writing (July 2020) use of midurethral tapes is not permitted in the NHS or in PURSUIT. _x000D_ _x000D_ We do not know which of these treatments is best for women who have already had an operation or bulking injections for SUI. The aim of this study is to find out whether a surgical operation or endoscopic bulking injections are better for treating recurrent or persistent SUI. _x000D_ _x000D_ WHO CAN PARTICIPATE? _x000D_ Adult (18 years or older) women with recurrent or persistent SUI who have already had an operation or bulking injection for it. _x000D_ _x000D_ WHAT DOES THE STUDY INVOLVE? _x000D_ 250 women will be recruited to the study. Equal numbers of women will join an endoscopic bulking injection group or a surgical operation group. Which group women join will be decided by chance (in a process called randomisation). Women in the surgical operation group will decide which operation to have with their doctor. Women will receive their treatment and aftercare at hospital, as they would during normal NHS care and will be asked to complete a questionnaire booklet at the start of the study and again 6 months, 1, 2 and 3 years later. The questionnaires cover general health, urinary symptoms and the effect of those symptoms on everyday life and sex life. We will audio-record consultations where the PURSUIT study is discussed with women and interview some women to see how research is explained and understand how women manage after their treatment. _x000D_ _x000D_ WHAT ARE THE POSSIBLE BENEFITS AND RISKS OF PARTICIPATING? _x000D_ There is no additional risk to normal NHS practice of the endoscopic bulking injections or surgical operations, and neither are new or experimental. Women taking part will have the same risks as anyone having treatment for recurrent SUI. This includes the possibility that symptoms may not improve as much as women would like. The risks and benefits of each treatment will be explained by the doctors, and women will be provided with supporting information as per their hospital’s normal care pathway. _x000D_ _x000D_ Some people favour being part of research studies because of the close contact with research staff and the opportunity to share their opinions and experiences of their condition and treatments. _x000D_ Women will be offered a £10 voucher for completing their questionnaire at 1 year and another £10 voucher for completing their questionnaire at 3 years. _x000D_ _x000D_ WHERE IS THE STUDY RUN FROM? _x000D_ This study is sponsored by North Bristol NHS Trust. The Bristol Randomised Trials Collaboration (as part of the Bristol Trials Centre) at the University of Bristol is responsible for managing the study. We aim to run the study in at least 20 NHS Hospitals across the UK._x000D_ _x000D_ WHEN IS THE STUDY STARTING AND HOW LONG IS IT EXPECTED TO RUN FOR? _x000D_ The study started in April 2019 and will run for 6 years, until 2025.

Lay abstract: DESIGN: Two-arm RCT randomising women with recurrent stress urinary incontinence (SUI) between urethral bulking injections (endoscopic arm) or a surgical operation (surgical arm). _x000D_ SETTING: At least 20 specialist urogynaecology or functional urology units in UK hospitals. _x000D_ POPULATION: Adult women diagnosed with recurrent SUI. _x000D_ INCLUSION CRITERIA: Confirmed recurrent, or persistent, SUI which is bothersome; the patient is willing to consider interventional therapy. _x000D_ EXCLUSION CRITERIA: Predominant urgency incontinence; Pelvic organ prolapse; Neurological disease; Being treated for gynaecological or bladder cancer; Unresolved mesh exposure from midurethral tape (MUT); Pregnancy; Urethral diverticulum; Recent pelvic surgery; In another relevant study; Unable to give informed consent; previous artificial urinary sphincter (AUS) surgery. _x000D_ HEALTH TECHNOLOGIES: 1. Endoscopic arm; urethral bulking injections (e.g. Bulkamid, Deflux, Macroplastique). 2. Surgical arm; colposuspension, autologous fascial sling, midurethral tape (only if current NHS rules allow), artificial urinary sphincter. _x000D_ PRIMARY OUTCOME: Patient reported outcome measure (ICIQ-UI-SF) at 1 year after randomisation. _x000D_ SECONDARY OUTCOMES: ICIQ-UI-SF at 6 months, 2 & 3 years after randomisation; Patient Global Impression of Improvement (PGI-I) at 1, 2 & 3 years after randomisation; operative assessment measures (including hospital stay and return to usual activity); POP/Incontinence Sexual Function Questionnaire (PISQ-IR); adverse events of treatment/re-treatment; cost-effectiveness from an NHS and societal perspective in terms of Quality Adjusted Life Years (QALYs) and ICIQ-UI-SF at 1 year, and from an NHS perspective in terms of QALYs at 3 years; a qualitative study will evaluate patient experiences of the intervention, and clinicians' views. Semi-structured interviews will be conducted during feasibility, baseline and after the intervention. Theoretical purposive sampling will cover the population characteristics. _x000D_ SAMPLE SIZE: The minimum clinically important difference in ICIQ-UI-SF is 2 with distribution-based methods. In case 5% of patients randomised to surgery instead receive endoscopic therapy before 12 months, we reduced difference to detect to 1.9. Thus 250 women are needed to detect a difference in mean ICIQ-UI-SF at 12 months of 1.9 (assuming common standard deviation of 4.1) with 90% power and a significance level of 5%, allowing for 20% loss to follow-up. _x000D_ PATHWAYS: Patients will undergo evaluation and urodynamic testing as per NICE guidance. Women with recurrent or persistent SUI will be randomised to either the endoscopic or surgical treatment arm. In the surgical arm, the type of surgical intervention will be decided using the study PIL and a detailed discussion between the patient and surgeon, as per usual local NHS practice. In the endoscopic arm, single and repeat injections will be permitted. Due to the timescales, any crossover cases will generally receive retreatment after 1 year, and so are unlikely to affect the primary outcome. The study will assess whether endoscopic or surgical interventions achieve better symptomatic outcome and/or quality of life outcomes at 1 year and will follow women up to 3 years after randomisation to see if responses are sustained. _x000D_ TIMETABLE: Duration 6 years; 6 months set-up, 2 year recruitment, 3 year follow-up, and 6 months analysis/dissemination _x000D_ INTERNAL PILOT: After 6 months, we expect to have recruited 24 patients. The threshold below which the trial would be discontinued due to poor recruitment will be 13 patients.

Research activity codes: 6.4 SURGERY
Health categories: RENAL AND UROGENITAL