Intravesical Aminophylline to Facilitate Ureteroscopic Access in Children With Distal Ureteral Stones.

Intravesical Aminophylline to Facilitate Semi-Rigid Ureteroscopic Access in Children With Lower Ureteral Stones: A Prospective Randomized Double-Blind Placebo-Controlled Trial

This study will evaluate whether intravesical aminophylline can facilitate semi-rigid ureteroscopic access in children with distal ureteral stones when the first gentle attempt to enter the ureter is unsuccessful.

Children scheduled for semi-rigid ureteroscopy for distal ureteral stones will first undergo the standard gentle attempt to pass the ureteroscope through the ureteric orifice and intramural ureter. If access is achieved, the child will continue standard treatment and will not be randomized. If access is not achieved, the child will be randomized during the operation to receive either intravesical aminophylline or intravesical normal saline placebo.

The study solution will be instilled into the bladder for approximately 5 minutes, then drained, and a second gentle ureteroscopic access attempt will be made. The main outcome is successful same-session passage of the intended semi-rigid ureteroscope without balloon dilation. The study will also assess the need for JJ stenting and deferred ureteroscopy, same-session stone treatment, operative outcomes, complications, and early aminophylline-related safety.

Study Overview

• Status: Recruiting
• Conditions: Ureteral Calculi; Pediatric Urolithiasis; Distal Ureteral Stone
• Intervention / Treatment: Drug: Aminophylline; Drug: Normal Saline Placebo

Detailed Description

This is a single-center, prospective, randomized, double-blind, placebo-controlled trial conducted at the Urology Department, Beni-Suef University Hospital.

The study population will include children with symptomatic distal ureteral stones who are scheduled for definitive treatment by semi-rigid ureteroscopy. All eligible children will undergo standard preoperative evaluation, including history taking, clinical examination, laboratory investigations, urine culture, imaging assessment, and anesthetic assessment.

During surgery, after cystoscopy and guidewire placement when feasible, the surgeon will make one standardized gentle attempt to pass a small semi-rigid ureteroscope through the ureteric orifice and intramural ureter. No forceful advancement, balloon dilation, ureteric orifice incision, or repeated traumatic manipulation will be allowed during this initial attempt. Children in whom the ureteroscope passes successfully will continue standard ureteroscopic treatment and will be recorded in a screening log but will not be randomized.

Only children with failed initial gentle negotiation will be randomized intraoperatively in a 1:1 ratio to one of two groups. The aminophylline group will receive intravesical aminophylline at a dose of 0.5 mg/kg diluted in 0.9% normal saline to a fixed total volume of 50 mL. The placebo group will receive 50 mL of 0.9% normal saline. The solution will be instilled through a urethral catheter, the catheter will be clamped for approximately 5 minutes, the bladder will then be drained, and a second gentle ureteroscopic access attempt will be made.

The surgeon, anesthetist, patient, family, and postoperative outcome assessor will remain blinded to treatment allocation. The study solution will be prepared by a clinician or pharmacist who is not involved in surgery or postoperative assessment.

If ureteroscopic access becomes possible after instillation, definitive ureteroscopic stone treatment will continue in the same session. If access remains unsuccessful, the surgeon will follow the predefined rescue plan, which may include balloon dilation when judged safe, or JJ ureteral stenting with deferred ureteroscopy when dilation is unsafe, not feasible, or unsuccessful. Forceful ureteroscope advancement will not be allowed at any stage.

The primary outcome is successful passage of the intended semi-rigid ureteroscope through the ureteric orifice and intramural ureter after study instillation without balloon dilation. Secondary outcomes include the need for balloon dilation, the need for JJ stenting and deferred ureteroscopy, completion of definitive stone treatment in the same session, operative time, postoperative stenting, intraoperative ureteric injury, postoperative complications, stone-free status, need for auxiliary procedures, and early safety outcomes related to aminophylline.

Safety monitoring will include intraoperative and early postoperative cardiorespiratory monitoring. Heart rate and blood pressure will be recorded during the early peri-intervention period. Early serum theophylline levels will be measured in the first aminophylline-treated cases to document systemic exposure after local intravesical use. Any clinically significant unexpected adverse event, including arrhythmia, hemodynamic instability, seizure activity, or hypersensitivity, will be managed according to the study safety protocol.

Follow-up will include assessment in the immediate postoperative period, at 1 to 2 weeks, at approximately 4 weeks, and at approximately 3 months after surgery. Follow-up will assess postoperative recovery, pain, hematuria, fever or urinary tract infection, emergency visits or readmission, stent-related symptoms if a stent is inserted, stone-free status according to local imaging policy, delayed complications, and any need for secondary intervention.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hany F Badawy, MD; Phone Number: +201149525028; Email: Hanyfathy86@gmail.com
• Study Contact Backup: Name: Ahmed Gmal, Md; Phone Number: +20 11 18206022; Email: Drhanyfathy86@GMAIL.COM

Study Locations

• Egypt
  • Beni Suweif Governorate
    • Banī Suwayf, Beni Suweif Governorate, Egypt
      • Recruiting
      • Department of Urology- Beni-Suef University Hospitals
      • Contact: Hany F Badawy, MD; Phone Number: +201149525028; Email: Hanyfathy86@gmail.com
      • Principal Investigator: Hany F Badawy, MD
      • Contact: Ahmed Gmal, Md; Phone Number: +20 11 18206022; Email: Drhanyfathy86@GMAIL.COM

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Children older than 2 years and younger than 18 years.
• Single unilateral lower/distal ureteral stone confirmed by low-dose non-contrast computed tomography according to local policy.
• Stone size 5 to 15 mm.
• Candidate for definitive treatment by semi-rigid ureteroscopy.
• Sterile urine culture before surgery, or previously positive urine culture that has been properly treated before intervention.
• Intraoperative failed initial gentle negotiation of the ureteric orifice/intramural ureter according to the study definition.
• Written informed consent from the parent or legal guardian, with child assent when appropriate.

Exclusion Criteria:

• Known hypersensitivity to aminophylline, theophylline, or ethylenediamine.
• Use of oral or intravenous aminophylline or theophylline within the previous 24 hours.
• Pre-existing ipsilateral JJ ureteral stent.
• Stone peeping at the ureteric orifice.
• Congenital or acquired abnormality that may affect distal ureteric access, such as ureterocele, obstructive megaureter, distal ureteric stricture, previous ureteric reimplantation, or previous ipsilateral ureteral reconstruction.
• Known bladder dysfunction or conditions likely to affect normal bladder capacity.
• Multiple ipsilateral ureteral stones or associated renal stones requiring flexible ureteroscopy or a ureteral access sheath strategy.
• Febrile urinary tract infection, pyonephrosis, sepsis, or any case requiring urgent decompression instead of definitive ureteroscopy.
• Cardiac disease, arrhythmia, uncontrolled hypertension, hyperthyroidism, epilepsy or seizure disorder, or significant hepatic impairment.
• Inability to complete follow-up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravesical Aminophylline; Children with failed initial gentle semi-rigid ureteroscopic access will receive intravesical aminophylline 0.5 mg/kg diluted in 0.9% normal saline to a total volume of 50 mL. The solution will dwell in the bladder for approximately 5 minutes before drainage and a second gentle ureteroscopic access attempt.	Drug: Aminophylline; Aminophylline will be administered intravesically at a dose of 0.5 mg/kg, diluted in 0.9% normal saline to a fixed total volume of 50 mL. The solution will be instilled through a urethral catheter, retained in the bladder for approximately 5 minutes, then drained before a second gentle semi-rigid ureteroscopic access attempt.
Placebo Comparator: Intravesical Normal Saline Placebo; Children with failed initial gentle semi-rigid ureteroscopic access will receive 50 mL of intravesical 0.9% normal saline placebo. The solution will dwell in the bladder for approximately 5 minutes before drainage and a second gentle ureteroscopic access attempt.	Drug: Normal Saline Placebo; A 50 mL volume of 0.9% normal saline placebo will be instilled intravesically through a urethral catheter, retained in the bladder for approximately 5 minutes, then drained before a second gentle semi-rigid ureteroscopic access attempt.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With Successful Same-Session Semi-Rigid Ureteroscopic Access Without Balloon Dilation	Successful access is defined as passage of the intended semi-rigid ureteroscope through the ureteric orifice and intramural ureter after study solution instillation, without the need for balloon dilation. The outcome will be reported as the proportion of randomized participants achieving successful access in each study arm.	Intraoperative, immediately after 5-minute intravesical study solution instillation during the index ureteroscopy procedure.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Requiring Balloon Dilation	This outcome will assess the proportion of randomized participants who require balloon dilation after failure of the second gentle ureteroscopic access attempt following study solution instillation.	Intraoperative, during the index ureteroscopy procedure
Total Operative Time	Total operative time will be measured in minutes from the start of endoscopic instrumentation to completion of the index endoscopic procedure.	Intraoperative, during the index ureteroscopy procedure
Proportion of Participants Requiring Postoperative Ureteral Stenting	This outcome will assess the proportion of randomized participants requiring ureteral stent placement at the end of the index procedure according to predefined clinical criteria, including significant mucosal injury, false passage, perforation, marked ureteric edema, difficult instrumentation, residual stone burden, or surgeon concern regarding safe postoperative drainage.	At the end of the index ureteroscopy procedure
Proportion of Participants With Postoperative Complications	This outcome will assess postoperative complications including hematuria, pain requiring additional analgesia, fever, febrile urinary tract infection, emergency visit, readmission, or any complication graded according to the Clavien-Dindo classification.	From the end of surgery up to 3 months after the index procedure
Proportion of Participants With Stone-Free Status	Stone-free status will be assessed according to the local imaging policy. Participants will be considered stone-free if no residual ureteral stone requiring auxiliary or secondary intervention is detected during follow-up.	Up to 3 months after the index procedure

Collaborators and Investigators

• Sponsor: Beni-Suef University
• Investigators: Principal Investigator: Hany F Badawy, MD, Faculty of medicine BeniSuef University

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: May 25, 2026
• First Submitted That Met QC Criteria: May 25, 2026
• First Posted (Actual): June 1, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Intravesical Aminophylline; Semi-Rigid Ureteroscopy; Pediatric Ureteroscopy; Ureteroscopic Access; Distal Ureteral Stones
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Calculi; Pathological Conditions, Anatomical; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urolithiasis; Urinary Calculi; Ureteral Diseases; Pathological Conditions, Signs and Symptoms; Ureterolithiasis; Ureteral Calculi; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Amines; Purinones; Purines; Drug Combinations; Ethylenediamines; Diamines; Polyamines; Xanthines; Theophylline; Aminophylline
• Other Study ID Numbers: FMBSUREC05052026Badawy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared because this study involves pediatric individual-level clinical data. Only aggregated, de-identified study results will be reported. Any future sharing of de-identified individual participant data would require additional approval from the Research Ethics Committee.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No