Effect of Antihistamines on Ureteral Stent-Related Symptoms

Study Overview
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Brief Summary
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This is a prospective, double-blind, randomized, open-label, single-center trial of up to 78 participants who are adult patients (aged 18-80 years) and are undergoing unilateral retrograde ureteroscopy with planned ureteral stent placement for treatment of urinary tract stones. Eligible patients will be randomly and divided into two groups in a 1:1 ratio. Group A will receive fexofenadine 180 mg once daily in addition to standard of care treatment. Group B will receive placebo in addition to standard of care treatment. The routine standard of care treatment will consist of oral non-steroidal anti-inflammatory drugs (NSAIDs). The primary outcomes of the study are the Ureteral Stent Symptom Questionnaire (USSQ) urinary symptom score and pain score. Secondary outcomes include (i) number of office phone calls due to urinary symptoms; (ii) duration of analgesic use; (iii) duration and quantity of narcotic use; (iv) number of emergency department visits; (v) drug-related adverse effects; (vi) other domains of the USSQ.

Detailed Description
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Ureteral stents treat ureteral obstruction, allow for passive dilation of the ureter, maintain urine flow to the bladder, and aid in the recovery of the ureter after endoscopic surgery or ureteral injury. These stents are routinely utilized after urologic procedures for the treatment of urolithiasis and are generally kept in place for 1-2 weeks following the procedure. Despite their advantages, indwelling ureteral stents cause discomfort and reduce patient quality of life. These symptoms are partially attributed to local irritation to the ureter and bladder. Bothersome stent-related symptoms include urinary urgency, frequency, flank pain, hematuria, dysuria, sexual side effects, and emotional distress. The majority of patients with ureteral stents experience symptoms post-operatively. Several studies have indicated that agents such as antimuscarinics or alpha-1 adrenergic receptor antagonists may improve stent-related symptoms. The indications for anticholinergic medications are based on blocking involuntary bladder muscle contraction; however, the efficacy of these drugs is still controversial. Furthermore, these medications have potential adverse side effects. Antihistamines also show potential in alleviating stent-related symptoms. Multiple in vitro studies have shown H1 receptor activity involved both in ureteral peristalsis and in bladder contraction. Both first- and second-generation H1 antagonists have shown activity in the urinary tract. In clinical practice, antihistamines are commonly utilized in the management of bladder pain caused by interstitial cystitis. Additionally, a randomized controlled trial found efficacy of antihistamines for pain management in the setting of renal colic from obstructing ureteral stones. There is novel evidence that in patients with indwelling stents, there are inflammatory changes in the bladder with an associated eosinophilic reaction. Eosinophilic cystitis is commonly associated with bladder irritation or allergy, and these findings point to a novel paradigm of treating patients with antihistamines. To our knowledge, no studies have evaluated the efficacy of antihistamines for managing stent-related symptoms.

Official Title
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Effect of Antihistamines on Ureteral Stent-Related Symptoms: Randomized Controlled Trial

Conditions
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Nephrolithiasis

Intervention / Treatment
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* Drug: Fexofenadine Hcl 180Mg Tab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (aged 18-80 years) who are undergoing unilateral retrograde ureteroscopy with planned ureteral stent placement for treatment of urinary tract stones Exclusion Criteria: Preoperative use of antihistamines, beta-3 agonists, anticholinergics, corticosteroids, and chronic opioid analgesic use Preoperative indwelling ureteral stent at the time of treatment Neurogenic bladder, ureteral stricture, interstitial cystitis, or chronic prostatitis Pregnancy or breastfeeding Planned bilateral ureteroscopy Solitary or transplanted kidney Hypersensitivity to antihistamines Severe renal disease (glomerular filtration rate (GFR) < 10 ml/min or on dialysis) Significant deviation in operative plan (ureteral stent not deemed necessary, incidental urologic malignancy, tandem ureteral stent placement, second-stage procedure required)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomized in a 1:1 ratio to receive fexofenadine or placebo in addition to the standard of care. A total of 39 subjects will be randomized to each group.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fexofenadine<br>Participants in this arm will receive fexofenadine 180mg once daily, in addition to standard of care pain medications (NSAIDs). | Drug: Fexofenadine Hcl 180Mg Tab<br>* Fexofenadine 180mg tablet to be taken orally once a day until stent removal.<br>* Other names: Fexofenadine;|
| Placebo Comparator: Placebo<br>Participants in this arm will receive placebo once daily, in addition to standard of care pain medications (NSAIDs). | Drug: Placebo<br>* Placebo tablet to be taken orally once a day until stent removal.<br>* Other names: Placebo Tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in USSQ urinary symptom score | Ureteric Stent Symptoms Questionnaire (USSQ) is a self-administered questionnaire to evaluate the overall impact of ureteral stents on different aspects of life. Urinary symptom will be assessed at different time points. The urinary symptom section consists 11 questions. A sum of the total score can range from 11 to 54 points. High score indicates worse outcome. | At time of initial visit (prior to surgery - baseline), at time of stent removal (1-2 weeks after surgery), at time of follow-up (4-6 weeks after stent removal) | 
| Change in USSQ body pain score | Ureteric Stent Symptoms Questionnaire (USSQ) is a self-administered questionnaire to evaluate the overall impact of ureteral stents on different aspects of life. Body pain will be assessed at different time points. The body pain section consists 7 questions. A sum of the total score can range from 6 to 37 points. High score indicates worse outcome. | At time of initial visit (prior to surgery - baseline), at time of stent removal (1-2 weeks after surgery), at time of follow-up (4-6 weeks after stent removal) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of office phone calls due to urinary symptoms and pain | This is to measure the morbidity associated with the indwelling ureteral stent. Urinary symptoms will include urinary frequency, urgency, incontinence, nocturia, incomplete emptying, dysuria, and hematuria. | At time of stent removal (1-2 weeks after surgery) | 
| Duration of NSAID use | This is to measure morbidity associated with the indwelling ureteral stent. Duration will be reported in days. | At time of stent removal (1-2 weeks after surgery) | 
| Quantity of narcotic use | This is to measure the morbidity associated with the indwelling ureteral stent. It will be reported in milligram morphine equivalents. | At time of stent removal (1-2 weeks after surgery) | 
| Number of emergency department visits | This is to measure morbidity associated with the indwelling ureteral stent. Incidence will be collected at study visit. | At time of stent removal (1-2 weeks after surgery) | 
| Number of drug-related adverse effects | This is to measure the morbidity of the study drug. Incidence will be self-reported by patients. | At time of stent removal (1-2 weeks after surgery) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antihistamines, Ureteral stent