Effect of Antihistamines on Ureteral Stent-Related Symptoms
Effect of Antihistamines on Ureteral Stent-Related Symptoms
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.
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.
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)