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

Beni-Suef University

Status and phase: Enrolling; Phase 2

Conditions: Pediatric Urolithiasis; Distal Ureteral Stone; Ureteral Calculi

Treatments: Drug: Normal Saline Placebo; Drug: Aminophylline

Study type: Interventional

Funder types: Other

Identifiers

NCT07617896

FMBSUREC05052026Badawy

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 2 to 18 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 2 patient groups, including a placebo group

Intravesical Aminophylline

Experimental group

Description:

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.

Treatment:

Drug: Aminophylline

Intravesical Normal Saline Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Normal Saline Placebo