Clinical trial NCT06469736: Comparison Between Ureterorenoscopy with Lithotripsy Alone Versus Combination with Hydrogel for Kidney Stone Removal
Official title: Standard of Care Ureterorenoscopy with Lithotripsy Versus in Combination with the Hydrogel Method for Kidney Stone Removal: an Open, Randomized, Monocentric Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Nephrolithiasis
Lithotripsy, Laser
Ureteroscopy
Keywords: Hydrogel
MediNiK
Hydrogel methode
Stone Free Rate
Zero Residual Fragments
URS
Dusting
Stone free
Thulium
Kidneystones
Lead sponsor: Technical University of Munich
Sponsor class: OTHER
First posted: 2024-06-24
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The incidence of kidney stones (urolithiasis) has surged in both developing and developed countries, affecting approximately 15% of the global population. From 2010 to 2019, diagnoses of kidney and ureteral stones rose by 8% in Germany, 26% in France, and 15% in England. Correspondingly, the number of surgical stone removal procedures increased by 3%, 38%, and 18%, respectively. Common treatments include extracorporeal shock wave lithotripsy (ESWL), ureterorenoscopy (URS) with lithotripsy, and percutaneous nephrolithotomy (PCNL).

URS, depending on stone size, has become a preferred method due to advancements in intraoperative imaging and laser technology. Despite these improvements, small fragments often remain post-intervention, leading to recurrent stones. Complete removal of all fragments is crucial to significantly reduce recurrence rates. Current literature suggests a high recurrence rate with residual fragments, impacting healthcare costs and patient quality of life.

A key objective in endourological research is optimizing the stone clearance rate. Techniques like coagulum lithotomy and the autologous blood clot technique have been developed to enhance residual stone removal after laser fragmentation. These methods benefit selected patients but are not widely adopted due to complications such as reduced intraoperative visibility and long coagulum formation times.

Recently, a two-component hydrogel system called mediNiK® (Purenum GmbH, Germany) was developed. This biocompatible gel can be applied through an endoscope after stone fragmentation and large fragment retrieval to embed smaller fragments and dust, forming a removable conglomerate. MediNiK® has demonstrated effectiveness in embedding and removing stone residues and is already in clinical use in Europe, showing potential for optimizing stone removal.

A multicenter study has assessed the safety and tolerability of mediNiK® in standard URS (Open, randomized, multicentre study to evaluate the safety, tolerability, and performance of mediNiK® compared to standard treatment in kidney stone removal - DRKS00030532). Results indicate the gel is safe and tolerable. However, further data from larger cohorts and comparisons with conventional URS are necessary before widespread adoption of mediNiK®.

Detailed description: The incidence of kidney stones (urolithiasis) has increased in both developing and developed countries, affecting around 15% of the world's population (1). Between 2010 and 2019, the diagnosis of kidney and ureteral stones in Germany, France and England increased by 8%, 26% and 15% respectively, while the number of surgical procedures to remove stones increased by 3%, 38% and 18% respectively (2). Common surgical treatments for kidney stones include extracorporeal shock wave lithotripsy (ESWL), ureterorenoscopy (URS) with lithotripsy and percutaneous nephrolithotomy (PCNL).

Depending on the size of the stone, URS has sometimes established itself as the method of choice, not least thanks to improved intraoperative imaging and the further development of laser technology. Despite these innovations, small fragments can remain in the kidney post-intervention, which in turn can lead to new stone formation (recurrent stones). From a medical point of view, complete removal of all fragments is essential in order to significantly reduce the recurrence rate of affected patients. According to the current literature, the recurrence rate in the sense of so-called secondary stone formation is estimated to be high in the case of residual fragments (3), associated with associated costs for the healthcare system and restrictions in the quality of life of the affected patients.

A major goal of endourological research in this area is therefore to optimize the stone clearance rate. Procedures such as coagulum lithotomy or the "autologous blood coagel technique" have been developed to improve the removal of residual stones after laser-guided fragmentation. Selected patients can benefit from these techniques, but their widespread use is limited, particularly due to the often associated deterioration in intraoperative visibility and the long waiting times until coagulum formation (4). For this reason, a two-component hydrogel system called mediNiK® (Purenum GmbH, Germany) was recently developed. This gel, consisting of two biocompatible components, can be applied via the inserted endoscope in a controlled manner and under visualization after completion of stone fragmentation and retrieval of large fragments in order to embed smaller stone fragments and dust. The resulting conglomerate can then be removed using conventional grasping forceps (5).

The hydrogel method with mediNik® has proven to be effective in embedding and removing stone residues (6). The system is already being used clinically in Europe and shows great potential for optimizing stone removal. A safety assessment in a multicenter study has already shown that the use of the gel is safe and tolerable in the context of standard URS. (Open, randomized, multicentre study to evaluate the safety, tolerability and performance of mediNiK® compared to standard treatment in the removal of kidney stones - DRKS00030532 - https://drks.de/search/de/trial/DRKS00030532.) However, before mediNik® can be used across the board, further data in a larger cohort and, in particular, a comparison with conventional URS are required.

The primary objective of this study is to compare the standard URS for the treatment of kidney stones without and with mediNik® with regard to the postoperative stone clearance rate. Further secondary endpoints are described in chapter 4. The results should provide the central basis for optimizing stone therapy at European centers and thereby improving medical care while optimizing costs.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects aged ≥ 18 years
* Evidence of nephrolithiasis on presentation of a preoperative computer tomography (CT) scan not older than 6 months
* Minimum size of the kidney stones defined as \&gt;10mm in the longest axis in the preoperative CT.
* Ability to read, write and speak German
* Women of childbearing age must have a negative serum pregnancy test at the start of the study.
* Submission of a personally signed and dated informed consent form stating that the subject has been informed of all relevant aspects of the study prior to any trial-related activity and that all information has been understood

Exclusion Criteria:

* Participation in another clinical trial for kidney stone removal in the last 6 months
* Subjects with gastrointestinal cancer who have not been in remission for at least 2 years
* Subjects with a single kidney, horseshoe kidney or other anatomical abnormalities that may increase the risk of surgery for the subject
* Subjects with untreated ureteral stenosis or renal stenosis and narrow ureteropelvic junction/ureterovesical junction
* Subjects with known impaired renal function from stage IV or known dialysis
* Subjects with chronic hydronephrosis not associated with nephrolithiasis
* Subjects with the following known or suspected diseases: Coagulation disorders, untreated urinary tract infections, renal disease sepsis and marked prostatic hyperplasia
* Subjects with any other disease or condition that, in the opinion of the investigator, could interfere with the purpose of the study (e.g. bleeding that restricts vision in the kidney, problems in the renal tubular system)
* Breastfeeding or pregnant women
* Subjects who may be part of a vulnerable group (e.g. prisoners or developmentally delayed adults)

Primary outcomes:
measure: Stone free Rate after URS
timeFrame: From enrollment to postoperative follow-up at 2 months.
Secondary outcomes:
measure: Surgery Duration
timeFrame: During the procedure
measure: Laser duration
timeFrame: during the procedure
measure: Basketing duration
timeFrame: during the procedure
measure: Complication
timeFrame: after the procedure up to 1 month
measure: Subjective assessment of the operation by the surgeon
timeFrame: During the procedure
measure: Cost
timeFrame: From enrollment to postoperative follow-up at 12 months
measure: Frequency of a stone-related event
timeFrame: From enrollment to postoperative follow-up at 3 months.
Other outcomes:
Locations:
city: Munich
country: Germany
facility: University Hospital rechts der Isar
state: Bavaria
Study officials:
affiliation: Technical University of Munich
name: Michael Straub, Doctor
role: PRINCIPAL_INVESTIGATOR
References: