TISU (Therepeutic Intervention for Stones in the Ureter): ESWL versus Ureteroscopy, a multicentre RCT

Introduction & Objectives: Renal stone disease is common and can cause emergency presentation with acute pain due to ureteric colic. International guidelines have stated the need for a multi-centre Randomised Controlled Trial (RCT) to determine whether non-invasive outpatient (shock wave lithotripsy, SWL) or surgical( ureteroscopy, URS) intervention should be the first line treatment for those needing active intervention. This has implications for shaping clinical pathways. We report a pragmatic national multi-centre non-inferiority RCT comparing SWL with URS.
Materials & Methods: This trial tested for non-inferiority of up to two sessions of SWL compared to URS as initial treatment for ureteric stones requiring intervention. The primary outcome was whether further intervention was required to clear the stone, and secondary outcomes included quality of life assessment, severity of pain and serious complications; these were based on questionnaires at baseline, 8 weeks and 6 months. We included patients over 16 years with a single ureteric stone clinically deemed to require intervention. Intention-to-treat and Per-Protocol analysis were planned. Sites (n=25) were selected as high volume stone centres, with fixed site lithotripters to ensure equipoise in access to treatment arms. Ethical approval was granted by North of Scotland Ethics Committee (ref13/NS/0002) and local approval at each site. Randomisation was hosted centrally at ChART, Aberdeen.
Results: We recruited 613 participants from a total of 1291 eligible patients, over a 4 year period, randomising 306 to SWL and 307 to URS. Sixty-seven patients (22.1%) in the SWL arm needed further treatment compared to thirty-one patients (10.3%) in the URS arm. The absolute risk difference was 11.7%(95% CI 5.6%, 17.8%) in favour of URS, which was inside the 20% threshold we set for demonstrating non-inferiority of SWL.
Conclusions: This large RCT was designed to test whether SWL is non-inferior to URS, and confirmed this; although SWL is an out patient non-invasive treatment with potential advantages both for patients and reducing in patient health care resource use, the trial did show a benefit in overall clinical outcomes with URS compared to SWL, reflecting contemporary practice. The TISU study provides much sought Level 1 evidence to help guide choice of modality for this common health condition.