The clinical and cost effectiveness of surgical interventions for stones in the lower pole of the kidney: the PUrE RCT - Percutaneous Nephrolithotomy (PNL), Flexible Ureterorenoscopy (FURS) and Extracorporeal Shockwave Lithotripsy (ESWL) for lower pole calyceal kidney stones

Design: A pragmatic multicentre RCT, to determine the clinical and cost effectiveness of surgical interventions for stones in the lower pole calyces of the kidney: RCT 1: Flexible ureterorenoscopy with laser lithotripsy (FURS) versus Extracorporeal Shockwave Lithotripsy (ESWL) for stone sizes <=10mm; RCT 2: FURS versus Percutaneous Nephrolithotomy (PNL) for stones sizes >10mm <=25mm. Health technologies being assessed: 1) FURS: a flexible ureteroscope is passed into the kidney and a holmium laser fibre used to fragment stones. Stone fragments are then either retrieved or the patient passes them spontaneously after the procedure: 2) PNL: A small incision in made in the skin through which a tube is inserted into the kidney. A nephroscope is inserted via this tube to retrieve the stone, or fragment it before retrieval. The intention is to remove all stone fragments: 3) ESWL involves an external acoustic pulse (shockwave), from outside the body which is focused onto the kidney stone, causing it to fragment. Stone fragments are then passed spontaneously by the patient in the days following the treatment. It may be delivered by 'fixed' (static, on-site) or 'mobile' (external) machines. Setting: 50 Secondary care units across the UK Target Population: Adults with stones in the lower pole calyces of the kidney. Measurement of costs and outcomes: Primary Outcomes: 1) Generic Health Status (EQ-5D) area under the curve (AUC) to 3 months post intervention, based upon EQ-5D completion, at randomisation, pre-intervention, 1, 2, 4, 8, and 12 weeks post intervention, supplemented by patient initiated EQ-5D. 2) Incremental cost per quality adjusted life year (QALYS) gained at 12 months post randomisation based on the estimated NHS costs and participant responses to the EQ-5D. Secondary outcomes: SF12; pain (NRS); analgesic use (12 weeks post intervention and 12 months post randomisation); stone clearance, complications; additional interventions received; NHS use & costs; patient costs (out of pocket); (up to 12 months post randomisation). Sample size: The primary outcome is the AUC of the EQ-5D up to 3 months post intervention. To detect a 0.3 SD difference, 90% power, alpha 5%, 235 participants per group (470 total, 940 across strata) are required. Such a difference in generic health status is considered clinically relevant and in terms of treatment effect size, in the small to medium range as observed in other clinical studies. Allowing for 10% of participants with completely missing outcome data, where AUC cannot be calculated, we propose to randomise 522 participants in both RCT 1 and 2. Project timetable including recruitment rate: Start date 1st December 2015: Duration: 60 months. Milestones: prefunding: protocol development; MREC, Months: 1-5 Study initiation: NHS approvals, start site set up Months 6-24: establish study in 50 centres; months 6-40: identify and recruit participants; Months 41-54: complete 12 month follow up; Months 55-60: close down, analysis, report writing. Recruitment rate is based upon 2-3 eligible patients, with 1 recruited, per centre per month, across 50 centres. An internal pilot will confirm recruitment targets. Expertise: The strong, multidisciplinary, team comprises expert clinicians, a lay representative, trialists, a statistician and health economist, supported by CHaRT, a CTU, with a track record in delivering high-quality, large multicentre RCTs.