Oxybutynin for Post-surgical Bladder Pain and Urgency

Study Overview
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Brief Summary
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Bladder pain and urgency are common after bladder surgery. The objective is to determine if transdermal administration is superior to oral administration in alleviating pain and urgency.

Detailed Description
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Pain after bladder surgery is typically controlled with narcotics, non-steroidal anti-inflammatory medications, acetaminophen, regional anesthesia (caudal or epidural) and/or bladder muscle (detrusor) antispasmodic medication. It is often difficult to distinguish bladder pain from a sensation of urinary urgency and most likely patients are experiencing both sensations despite the bladder being empty from the indwelling catheter. Prior studies on adults have demonstrated the efficacy of preoperative oxybutynin and other antimuscarinics on decreasing catheter-related bladder discomfort in the postoperative period. For pediatric bladder surgery very few studies have been published. Intravenous ketorolac, epidural and caudal analgesia and intravesical ropivacaine have been shown to decrease postoperative bladder spasms. Intravesical oxybutynin has been used in the operating room in adults to decrease post-operative ureteral stent pain. For open bladder surgery the current pain management standard is intra- and postoperative ketorolac (Q6hrs) and acetaminophen and narcotic as needed. Oral oxybutynin is started pre-operatively and then continued post-operatively every 8 hours. Unfortunately, the bioavailability of oral oxybutynin is poor due to first pass (liver) metabolism of the absorbed medication and a subsequent high level of desethyloxybutynin (DEO) produced by the liver. DEO, responsible for most of the side effects such as dry mouth, dizziness, over-heating, drowsiness and constipation. This metabolite and side effects are less with the transdermal route. A prior retrospective analysis of children by the investigators did not show a difference in pain between starting oral oxybutynin pre-operatively or initiating medication post-operatively. Whether this was due to no difference, insufficient patient numbers or inability to distinguish bladder spasms from pain is unknown. That study employed the Wong-Baker-Facies scale for pain measurement in children. At the time of that study there was no valid scale for objective measurement of bladder urgency in adults or children. Over the last five years the investigators have developed a validated scale (IRB 647657, 638967) that will allow for a better measure and distinguish bladder and incisional pain from bladder spasms/urgency. The objective is to determine if transdermal administration is superior to oral administration in alleviating pain and urgency after bladder surgery in children. Oral oxybutynin is a commonly used treatment in children with neuropathic bladder dysfunction and for adults with overactive bladder (OAB) and incontinence. As mentioned, transdermal administration has higher bioavailability and a lower adverse event profile. Transdermal administration has been shown to be safe and efficacious in children with neuropathic bladder disease. The hypothesis is that the transdermal route will decrease bladder pain and urgency if applied prior to surgery with a lower side effect profile. Based upon the power analysis by Blythe Durbin-Johnson, Ph. D. The investigators plan to evaluate up to 100 patients with early termination if endpoints are reached before 100 subjects. Outcomes will be compared between groups using two-sample t-tests if the outcome is sufficiently normally distributed, and Wilcoxon-rank sum tests otherwise. With 60 subjects divided among two groups, the two-sample t-test will have 80% power to detect a 0.74 standard deviation difference in outcomes.

Official Title
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Oxybutynin for Post-surgical Bladder Pain and Urgency

Conditions
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Overactive Bladder Syndrome, Neuropathic Bladder

Intervention / Treatment
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* Drug: Oxybutynin Transdermal Patch
* Drug: Oral Oxybutynin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who will undergo bladder surgery that requires an indwelling bladder catheter after surgery. Age Range: Four to 8 years of age are eligible for the study. Exclusion Criteria: Patients who have had prior bladder surgery. Patients who have neurologic disease that could impair bladder sensation. Patients who are already taking antimuscarinic or antispasmodic medications. Patients with glaucoma, any neurologic disease, dementia, impaired mentation or disorder of the central nervous system. Patients taking any medication that affects the central nervous system such as antidepressant, anxiolytic or antipsychotic medications. Less than four years of age cannot have the transdermal patch due to fixed dose. Over 8 years of age: less than 5% of our patients, who undergo this surgery, are over 8 years of age and is usually a rare adolescent. Data in an older cohort may confuse the results since they respond differently to bladder surgery due to larger incision and longer hospital stay with a catheter.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 8 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Group A: Oral Administration Current standard treatment at U.C. Davis Children's Hospital Oral oxybutynin (5mg) is administered in the preoperative area prior to surgery. Our current regimen is to mix the oxybutynin with the standard preoperative Versed so children do not have to take two dosages. Post-operatively oral oxybutynin (5mg) is administered every 8 hours in the hospital. Group B: Transdermal Administration Guardian will be given the transdermal patch (3.9mg oxybutynin) at the preoperative appointment with instructions to apply the day prior to surgery. While in the hospital no oral oxybutynin will be prescribed.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oral administration<br>Oral oxybutynin (5mg) is administered in the preoperative area prior to surgery. The current regimen is to mix the oxybutynin with the standard preoperative Versed so children do not have to take two dosages. Post-operatively oral oxybutynin (5mg) is administered every 8 hours in the hospital. | Drug: Oral Oxybutynin<br>* Oral administration of oxybutynin (5mg) every 8 hours in the hospital.<br>* Other names: Ditropan XL;|
| Experimental: Transdermal administration<br>Guardian will be given the transdermal patch (3.9mg oxybutynin) at the preoperative appointment with instructions to apply the day prior to surgery. While in the hospital no oral oxybutynin will be prescribed. | Drug: Oxybutynin Transdermal Patch<br>* Transdermal patch of oxybutynin will be used instead of oral oxybutynin.<br>* Other names: Ditropan XL;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urgency Scores | Mean and peak urgency scores measured using the Pictorial Scale of Bladder Urgency. Children will choose one of four illustrations depicting bladder urgency. These illustrations have been assigned a number 1 through 4. The score of 1 indicates less urgency and a score of 4 indicating greatest urgency. | Preoperative (one week to two months) to postoperative period (six weeks). | 
| Pain Scores | Mean and peak pain scores assessed using current standard University of California, Davis Medical Center protocols in the preoperative and postoperative period. Depending upon the age of the child and development, the Wong-Baker-Facies scale or numerical scale will be utilized in the hospital, both scored on a scale from 0 to 10, with higher scores indicating greater pain. | Preoperative (one week to two months) to postoperative period (six weeks). | 
| Narcotic Usage | Narcotic usage will be assessed. Morphine and hydrocodone in mg/kg will be recorded and evaluated over the hospitalization period. | Postoperative (six weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transdermal Oxybutynin