Clinical trial NCT04726345: Effect of Antihistamines on Ureteral Stent-Related Symptoms
Official title: Effect of Antihistamines on Ureteral Stent-Related Symptoms: Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nephrolithiasis
Keywords: Antihistamines
Ureteral stent
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Coloplast A/S
First posted: 2021-01-27
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change in USSQ urinary symptom score
timeFrame: 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)
measure: Change in USSQ body pain score
timeFrame: 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 outcomes:
measure: Number of office phone calls due to urinary symptoms and pain
timeFrame: At time of stent removal (1-2 weeks after surgery)
measure: Duration of NSAID use
timeFrame: At time of stent removal (1-2 weeks after surgery)
measure: Quantity of narcotic use
timeFrame: At time of stent removal (1-2 weeks after surgery)
measure: Number of emergency department visits
timeFrame: At time of stent removal (1-2 weeks after surgery)
measure: Number of drug-related adverse effects
timeFrame: At time of stent removal (1-2 weeks after surgery)
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Irving Medical Center/NYP
state: New York
Study officials:
affiliation: Professor of Urology
name: Ojas Shah, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aboutaleb H, Gawish M. Correlation of Bladder Histopathologic Changes Due to Double-J Stenting to the Period of Stenting: A Preliminary Study. J Endourol. 2017 Jul;31(7):705-710. doi: 10.1089/end.2017.0113. Epub 2017 May 31.
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citation: Joshi HB, Stainthorpe A, MacDonagh RP, Keeley FX Jr, Timoney AG, Barry MJ. Indwelling ureteral stents: evaluation of symptoms, quality of life and utility. J Urol. 2003 Mar;169(3):1065-9; discussion 1069. doi: 10.1097/01.ju.0000048980.33855.90.
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citation: Sivalingam S, Streeper NM, Sehgal PD, Sninsky BC, Best SL, Nakada SY. Does Combination Therapy with Tamsulosin and Tolterodine Improve Ureteral Stent Discomfort Compared with Tamsulosin Alone? A Double-Blind, Randomized, Controlled Trial. J Urol. 2016 Feb;195(2):385-90. doi: 10.1016/j.juro.2015.08.104. Epub 2015 Sep 21.
citation: Yilmaz E, Batislam E, Deniz T, Yuvanc E. Histamine 1 receptor antagonist in symptomatic treatment of renal colic accompanied by nausea: two birds with one stone? Urology. 2009 Jan;73(1):32-6. doi: 10.1016/j.urology.2008.08.494. Epub 2008 Oct 11.