Access Sheaths With Aspiration for Renal RetrOgrade Surgery, Randomized CompArative Outcomes

BACKGROUND AND RATIONALE

Urinary lithiasis (kidney stone disease) affects approximately 10-15% of the population in developed countries and is characterized by high recurrence rates. Among surgical treatment options, retrograde intrarenal surgery (RIRS) using flexible ureteroscopy has become the standard-of-care approach for intrarenal stones measuring 1-3 cm, offering the advantages of a minimally invasive endoscopic approach combined with laser lithotripsy.

Ureteral access sheaths (UAS) are devices placed transurethrally prior to flexible ureteroscopy to facilitate repeated scope insertion, maintain stable ureteral access, and reduce intrapelvic pressure during the procedure. Two fundamentally different UAS designs are currently in clinical use at the study centre: (1) standard rigid sheaths, represented by the Navigator® (Boston Scientific), and (2) a novel vacuum-assisted flexible sheath, the ClearPetra® (Coloplast), which incorporates continuous negative-pressure aspiration to actively evacuate stone fragments and irrigation fluid throughout the procedure.

The theoretical advantages of vacuum-assisted UAS include improved intraoperative visibility due to continuous fluid evacuation, more efficient fragment extraction (particularly smaller dust-like fragments generated by laser pulp), potentially reduced intrapelvic pressure, and lower risk of infectious complications related to high intrarenal pressure. However, despite these mechanistic rationales and promising preliminary data, no randomised controlled trial has yet conclusively established the superiority of ClearPetra® over standard rigid sheaths in terms of stone-free rate for intrarenal lithiasis in the 1-3 cm range.

The current choice between sheath types at most urology departments - including the study centre - is made based on surgeon preference, device availability, or extrapolation from observational studies with significant methodological limitations. This genuine clinical equipoise justifies conducting a prospective randomised trial to generate Level I evidence on this clinically important question.

STUDY DESIGN

This is a prospective, single-centre, randomised controlled superiority trial with parallel groups and single-blind (outcome assessor-blinded) design. Patients are allocated in a 1:1 ratio to one of two treatment arms:

Experimental arm: Flexible ureteroscopy (RIRS) using ClearPetra® ureteral access sheath (Coloplast) - a flexible, vacuum-assisted sheath providing continuous negative-pressure aspiration.

Control arm: Flexible ureteroscopy (RIRS) using Navigator® ureteral access sheath (Boston Scientific) - a standard rigid sheath without active aspiration.

Both devices are CE-marked, commercially available, and currently used in routine clinical practice at Hospital Universitario Virgen del Rocío (Seville, Spain).

DEVICES UNDER INVESTIGATION

ClearPetra® (Coloplast): A tip-flexible ureteral access sheath designed for use with flexible ureteroscopes. Its distinctive feature is an integrated vacuum aspiration system that enables continuous active removal of stone fragments and irrigation fluid during the procedure. The sheath flexibility is intended to reduce trauma during insertion and improve conformability within the upper urinary tract.

Navigator® (Boston Scientific): A conventional rigid ureteral access sheath representing the current standard of care. It facilitates ureteroscope passage and provides a working channel for irrigation, but does not incorporate an active aspiration mechanism. Fragment removal depends on passive irrigation and the use of accessory instruments (baskets, stone cones).

Both devices are available in standard sizes compatible with the flexible ureteroscopes used at the study centre.

RANDOMISATION AND ALLOCATION CONCEALMENT

The randomisation sequence will be computer-generated using Randomizer.org (www.randomizer.org) prior to study initiation, producing a list of 156 consecutive assignments in a 1:1 ratio between the two arms. The sequence will be prepared before the first patient is enrolled.

Allocation concealment will be implemented via sequentially numbered, opaque, sealed envelopes prepared by an investigator not involved in patient recruitment or surgical procedures. Envelopes will be stored under lock and key in the principal investigator's office until the moment of use.

At the time of hospital admission for the scheduled surgical procedure, after confirming all eligibility criteria, the principal investigator or designated delegate will open the envelope corresponding to the patient's sequential number, revealing the assigned sheath type. This information will be communicated to the surgical team immediately before the endoscopic procedure begins. The date and time of each envelope opening will be recorded on a separate control sheet to ensure traceability.

BLINDING

Due to the physical nature of the surgical intervention, blinding of the surgeon and patient to treatment allocation is not feasible. However, single-blind design will be implemented at the level of outcome assessment:

CT outcome assessor: The urologist(s) responsible for analysing CT images to determine residual stone volume and stone-free status will be blinded to treatment allocation. Radiological images will be coded with a study number without any identification of the sheath type used.

Complications assessor: The investigator responsible for recording and classifying postoperative complications according to the Clavien-Dindo scale will also be blinded to group assignment.

This assessor-blinding strategy is the recognised standard approach in surgical device trials and is sufficient to ensure validity of the primary outcome, which is based on objective CT measurement.

SURGICAL PROTOCOL

All procedures will be performed by 2-3 urological surgeons at the study centre, each with extensive experience in flexible ureteroscopy (\>100 RIRS procedures performed). Both study devices are already part of these surgeons' routine clinical practice, ensuring no learning curve bias.

A standardised intraoperative protocol will be followed by all participating surgeons regardless of the assigned sheath, including:

Criteria for complete stone fragmentation

Systematic use of accessory instruments (retrieval basket, stone cone) according to fragment size

Predefined criteria for procedure completion

Standardised management of intraoperative complications

Randomisation will be performed immediately before the intervention, minimising the time during which the surgeon is aware of the assignment prior to the procedure. The primary outcome variable (CT-assessed SFR at one month) is an objective measure independent of the surgeon's intraoperative assessment.

An intraoperative registration form specific to the study will be completed by the operating surgeon immediately after each procedure, recording: procedure start and end times, active fragmentation time, laser activation time, fluoroscopy time, laser energy type and parameters used, accessory instruments employed, immediate endoscopic and fluoroscopic assessment of stone-free status, ureteral stenting decisions, and any intraoperative complications.

FOLLOW-UP SCHEDULE

Patients will be followed prospectively from the date of the intervention through 3 months post-surgery, with pre-specified evaluation time points:

OUTCOME MEASURES - TECHNICAL DEFINITIONS

Primary outcome - Stone-Free Rate (SFR) at 1 month: Defined as complete absence of residual lithiasis or presence exclusively of fragments ≤2 mm on non-contrast abdomino-pelvic CT performed at 30 ±7 days post-intervention. This is a dichotomous variable (yes/no stone-free). The CT assessor will be blinded to treatment allocation.

CT measurements will follow a standardised imaging protocol: multiplanar reconstruction (axial, coronal, sagittal), identification of all stone/fragment foci, measurement of maximum diameter in any plane, manual volumetric calculation, and density measurement at the point of maximum attenuation in Hounsfield Units (HU). All volumetric and dimensional measurements will be performed by a single experienced urological radiologist/assessor who is blinded to the assigned sheath type.

Sensitivity analysis for the primary outcome: A pre-specified sensitivity analysis will apply a stricter stone-free definition (complete absence of any residual fragment, 0 mm threshold) to evaluate consistency of results.

Secondary efficacy outcomes include:

Stone volume reduction rate at 1 month: calculated as \[1 - (residual postoperative volume / preoperative volume)\] × 100 (%)

• Stone-Free Rate (SFR) at 3 Months Post-Intervention [Срок оценки: 90 days (±14 days) after surgical intervention]
• Stone Volume Reduction Rate at 1 Month [Срок оценки: 30 days (±7 days) after surgical intervention]
• Immediate Endoscopic Stone-Free Rate [Срок оценки: Intraoperative (at procedure completion, Day 0)]
• Immediate Fluoroscopic Stone-Free Rate [Срок оценки: Intraoperative (at procedure completion, Day 0)]
• Retreatment Rate at 3 Months [Срок оценки: Up to 90 days (±14 days) after surgical intervention]
• Total Surgical Time [Срок оценки: Intraoperative (Day 0)]
• Active Stone Fragmentation Time [Срок оценки: Intraoperative (Day 0)]
• Fluoroscopy Time [Срок оценки: Intraoperative (Day 0)]
• Laser Activation Time [Срок оценки: Intraoperative (Day 0)]
• Rate of Ureteral Access Sheath Passage Failure Requiring Pre-Stenting [Срок оценки: Intraoperative (Day 0)]
• Immediate Postoperative Complications (≤30 Days) [Срок оценки: Up to 30 days after surgical intervention]
• Late Postoperative Complications (>30 Days to 3 Months) [Срок оценки: From 30 days to 90 days (±14 days) after surgical intervention]