Adjustable Anchored Single-Incision Mini-Slings Versus Standard Tension-Free Mid-Urethral Slings in the Surgical Management Of Female Stress Urinary Incontinence; A Pragmatic Multicentre Non–Inferiority Randomised Controlled Trial: The SIMS Trial.

Design: A pragmatic multicentre non–inferiority randomised controlled trial comparing adjustable anchored single-incision mini-slings (SIMS) with standard tension free mid-urethral slings (SMUS) in women with Stress urinary incontinence (SUI). Setting: Twenty-five secondary and tertiary units across UK. Target Population: Women aged 18 years or over with SUI, for whom surgery has been indicated. All women will have failed or declined conservative treatment (supervised pelvic floor muscle training - PFMT). Women who have had previous continence surgery, anterior or apical Prolapse (>/= stage 2, pre-dominant overactive bladder (OAB) symptoms and/ or concomitant surgery will be excluded. Intervention: 1) Adjustable Anchored single-incision mini-slings (SIMS); and 2) tension-free standard mid-urethral slings (SMUS) including retropubic tension free vaginal tapes (RP-TVT) and transobturator tension free vaginal tapes (TO-TVT). Outcome Measures: This RCT will assess and compare adjustable anchored SIMS vs. tension-free SMUS with respect to: patient reported success rates; objective success rates; impact on urinary symptoms; women’s health related QOL; sexual function and costs to health services up to 3 years follow-up. We will use the same assessment tools and QOL instruments that were used in our pilot RCT which observed a 97% response rate. Primary outcome measures: 1.The primary outcome measure will be patient reported success rates measured by the validated patient global impression of improvement index (PGI-I) at 12-months. 2.The primary economic outcome will be incremental cost per QALY gained at 12-months. The above measures will be also be assessed at 2&3 years. Secondary outcome measures: 1.Peri-operative complications including: lower urinary tract injuries; haemorrhage (blood loss >/= 200mls); post-operative voiding dysfunction; other complications. 2.Post-operative pain using a pain Numerical Rating Scale (NRS): assessed day 1-14. 3.Objective success rates: assessed by 24 hour pad test at 12 month and yearly upto 3 years. 4.Other Lower urinary tract symptoms using the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) at 3 & 12-months and yearly upto 3 years. 5.Health-related QOL profile (area under the curve) derived from EQ-5D, pain scores and ICIQ-FLUTSqol measurements at 4-weeks, 3 & 12-months and yearly upto 3 years 6.Recurrence of SUI, re-operation rates for SUI, further treatment received such as physiotherapy, medical treatment. 7.Secondary economic outcomes include; -NHS and patient primary and secondary care resource use and costs at 3-months; 12-months and yearly up to 3 years. -Incremental cost-effectiveness derived from responses to the ICIQ-FLUTSqol over the follow-up period at 12-months and yearly up to 3 years. -Incremental net benefit (NB) calculated from the responses to the discrete choice experiment (DCE) at 12-months. Sample size: The proposed trial design is non-inferiority so the sample size calculations reflect this. Published literature suggests that the P1, the percentage success rate at 12-months in the SMUS arm will be about 85%. Similar results were obtained from our pilot RCT. Power estimates were explored by simulating trials of fixed sample size (using equal allocation) with binary responses generated by P1=85% and P2=85%. Power was then estimated as the proportion of simulated trials where the lower bound of the 2-sided confidence interval satisfied P1-P2 > -10%. Simulations, run in Stata 11.2, show that a trial of 275/arm or 550 in total is required for the lower bound of the estimated 95% confidence interval to rule inferiority at the specified level with 90% power. Adjustment for potential 15% drop-out inflates the trial to 650 in total. For comparison, For comparison, a trial of this size would have above 80% power to test superiority on secondary outcomes of difference in means of size one quarter of a standard deviation. Project timetables & recruitment rate: Milestones are pre-funding: multicentre research ethics and central R&D approvals; months 1-6: study set-up authorisations; months 7-18: centre recruitment; months 7-44: recruit patients staggering centre start up (n=650); months 19-72: complete follow-up; months 73-78: close down and analysis.