Effect of Antihistamines on Ureteral Stent-Related Symptoms

Phase 2

Completed

• Conditions: Nephrolithiasis
• Interventions: Drug: Fexofenadine Hcl 180Mg Tab; Drug: Placebo

• Registration Number: NCT04726345
• Lead Sponsor: Columbia University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2021-01-20
• Study First Submitted QC: 2021-01-26
• Study First Posted: 2021-01-27
• Study Start: 2021-06-29
• Primary Completion: 2024-06-30
• Study Completion: 2024-06-30
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-30
• Last Update Posted: 2024-08-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 78

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fexofenadine	Fexofenadine Hcl 180Mg Tab	Participants in this arm will receive fexofenadine 180mg once daily, in addition to standard of care pain medications (NSAIDs).
Placebo	Placebo	Participants in this arm will receive placebo once daily, in addition to standard of care pain medications (NSAIDs).

Primary Outcome Measures

Name	Time	Method
Change in USSQ body pain score	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)	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.
Change in USSQ urinary symptom score	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)	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.

Secondary Outcome Measures

Name	Time	Method
Number of drug-related adverse effects	At time of stent removal (1-2 weeks after surgery)	This is to measure the morbidity of the study drug. Incidence will be self-reported by patients.
Number of office phone calls due to urinary symptoms and pain	At time of stent removal (1-2 weeks after surgery)	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.
Duration of NSAID use	At time of stent removal (1-2 weeks after surgery)	This is to measure morbidity associated with the indwelling ureteral stent. Duration will be reported in days.
Quantity of narcotic use	At time of stent removal (1-2 weeks after surgery)	This is to measure the morbidity associated with the indwelling ureteral stent. It will be reported in milligram morphine equivalents.
Number of emergency department visits	At time of stent removal (1-2 weeks after surgery)	This is to measure morbidity associated with the indwelling ureteral stent. Incidence will be collected at study visit.

Trial Locations

Locations (1)

Columbia University Irving Medical Center/NYP; 🇺🇸 New York, New York, United States