Title: 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
Funder: Chief Scientist Office, Scotland

Abstract: 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.

Lay abstract: Kidney stone disease is very common and although stones in the kidney do not always cause problems most need treatment. They can cause serious problems, such as pain, infection, and kidney failure, with burden to patients, the NHS and society. Many stones occur in the lower part of the kidney (lower pole stones - LPS) and are difficult to treat. There are 3 treatment options in the NHS:: 1) Flexible ureterorenoscopy with laser lithotripsy (FURS) - a small telescope is passed into the bladder through the water pipe, and up to the kidney, a laser beam breaks the stone into pieces; 2) Percutaneous nephrolithotomy (PNL) - a hole is made in the skin, a tube is inserted though it into the kidney. A telescope is inserted into the kidney via the tube to break the stone and remove all the pieces; 3) Extracorporeal shockwave lithotripsy (ESWL) - shockwaves from a machine outside the body target and break the stone into pieces, the pieces are passed by patients through the water pipe. ESWL does not need an anaesthetic, nor hospital stay, but passing the pieces can take time, more than one treatment may be needed for larger stones, and some pieces may not pass at all. PNL usually clears the stone completely in one go, but needs an anaesthetic, hospital stay, and may cause more serious problems (bleeding and infection). We think FURS may clear the stone more efficiently than ESWL, but less well than PNL, (as uses smaller telescope). FURS needs an anaesthetic, sometimes a hospital stay, has a small risk of complications (eg infection, bleeding). We are uncertain which of these treatments is best at getting rid of the stone and which is best value for patients and the NHS. They each have advantages and disadvantages (benefits and harms). There is little good quality data from studies that have directly compared the treatments and very little data on the impact of the treatments on patient’s health, to allow patients and their urologist to make the best decision about treatment. We propose giving 1) FURS or ESWL to 522 people with smaller LPS and 2) FURS or PNL to 522 people with larger LPS who agree to take part. They will be randomly allocated to the treatments to remove their stones. The study will cover a network of UK hospitals over 60 months, with each participant studied for 1 year. We will measure the impact of the treatments on their health, pain experienced, what additional treatments are needed, complications and the costs of treatment to patients and the NHS. We will assess whether we can recruit to the study during the first 15 months and make any changes necessary. Our research team includes specialists (urologists) who perform the procedures, a lay expert and experts in the design, performance and analysis of clinical trials. The study will be managed by a Clinical Trials Unit (CTU) very experienced at running large multicentre trials within the NHS. We have the support of the national organisation of doctors who treat stones. The study will take 5 months to set up; 35 months to start the centres, recruit participants and deliver the interventions, 14 months to complete the follow up and 6 months to analyse, write up. The costs of the study reflect staff and resources needed. We need a team of specialist nurses across the study hospitals to recruit organise and complete the study, a trial manager, plus the necessary experts in urology, trial design, statistics, economics, other costs include questionnaires and travel

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