Nitrous Oxide for Analgesia During Office Urethral Bulking

Study Overview
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Brief Summary
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This study is designed to determine primarily if there is a difference in perceived pain in patients receiving urethral bulking with calcium hydroxylapatite using local lidocaine versus local lidocaine plus nitrous oxide gas. Patients will be randomized to a control group (local lidocaine plus room air) or a intervention group (local lidocaine plus 50% nitrous oxide/50% oxygen inhaled mixture). Their pain will be assessed immediately after the procedure, and their recollection of pain will also be assessed at their 2 week post-procedure visit. There are other secondary outcome measures as well; please see outcome measures section for full description.

Official Title
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Nitrous Oxide for Analgesia During Office Urethral Bulking: a Randomized, Controlled Trial

Conditions
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Pain, Stress Incontinence, Female

Intervention / Treatment
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* Drug: Nitrous Oxide + Oxygen Gas (Product)
* Drug: lidocaine gel 2%
* Other: Room air


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients greater than or equal to 18 years old with demonstrable stress incontinence on supine stress test undergoing calcium hydroxylapatite injection for urethral bulking for the first time able to consent to the study and procedure Exclusion Criteria: < 18 years old prior urethral bulking therapy predominant urge incontinence symptoms contraindications to nitrous oxide pre-existing significant cardiopulmonary disease hypotension defined as systolic blood pressure (BP) < 90 or diastolic BP <50 on initial BP in the office chronic pain disorders (specifically fibromyalgia, chronic pelvic pain, sciatica or chronic low back pain, painful bladder syndrome) chronic narcotic use (defined as taking a narcotic medication >3 days per week during the past two weeks) pregnancy conditions of air trapping (bullous emphysema, bowel obstruction, pneumothorax, intracranial air, middle ear conditions, status post recent diving, recent eye surgery) lidocaine allergy neurologic diseases impairing pain perception.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Female

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: Randomized controlled trial with patients randomized 1:1 into two groups
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control group<br>lidocaine gel injected in the urethra 10 minutes prior to calcium hydroxylapatite injection plus self-administered room air | Drug: lidocaine gel 2%<br>* 6mL of 2% lidocaine gel will be inserted and injected into the urethral canal approximately 10 minutes prior to the procedure for each participant regardless of group assignment.<br>* Other names: Uro-Jet;Other: Room air<br>* Room air will be administered via the Pro-Nox machine to participants in the control group, starting just before the beginning of the urethral bulking procedure.<br>|
| Experimental: Study group<br>lidocaine gel injected in the urethra 10 minutes prior to calcium hydroxylapatite injection + self-administered Pro-Nox 50% nitrous oxide/50% oxygen. | Drug: Nitrous Oxide + Oxygen Gas (Product)<br>* Self-administered 50% nitrous oxide / 50% oxygen mixture will be given to the intervention group, starting just before the beginning of the urethral bulking procedure.<br>* Other names: Pro-Nox;Drug: lidocaine gel 2%<br>* 6mL of 2% lidocaine gel will be inserted and injected into the urethral canal approximately 10 minutes prior to the procedure for each participant regardless of group assignment.<br>* Other names: Uro-Jet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain | Pain will be assessed both before the procedure upon enrollment immediately after the procedure using a 10cm visual analog scale (VAS), where patients will mark their pain level along the scale from no pain at 0cm to pain as bad as it possibly could be at 10cm; the change in pain score between the before and after procedure VASs (i.e. the baseline pain score subtracted from the post-procedure pain score) is the primary outcome | upon enrollment and immediately after the procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recollection of change in pain | Recollection of pain measured by a 10cm visual analog scale (VAS) completed 10 minutes after the procedure; this will be compared to the baseline pain score on VAS from prior to the procedure, again to determine the patient's perceived change in pain during the procedure. The VAS used has patients mark their pain level along the scale from no pain at 0cm to pain as bad as it possibly could be at 10cm. The score on the VAS at baseline is subtracted from the score on the VAS at 10 minutes to get the change in pain as the patient remembered it. | 10 minutes after the procedure | 
| Procedure time | Time from the initial insertion of the cystoscope (for the injection of calcium hydroxylapatite) to final removal of the cystoscope | Intra-procedure | 
| Change in Urogenital Distress Inventory (UDI-6) score | A change in the patient's UDI-6 score, measured prior to procedure and then again at the 1-2 week post-procedure visit. UDI-6 is a measure of the severity of urinary symptoms the patient experiences, with minimum score of 0 (indicating no bother from urinary symptoms) and maximum score of 100 (indicating maximum bother from urinary symptoms). We will be assessing the change in this score from baseline, by subtracting the post-procedure score at 1-2 weeks from the baseline score. | at enrollment and then again at the patient's 1-2 week post-procedure visit. | 
| Change in Incontinence Severity Index (ISI) score | A change in the patient's ISI score, measured prior to procedure and then again at the 1-2 week post-procedure visit. ISI score measures severity of incontinence symptoms on a scale of 0 to 12, where 0 is no symptoms and 12 is maximal incontinence symptoms. We will calculate the change in score by subtracting the post-procedure score at 1-2 weeks from the baseline score. | at enrollment and then again at the patient's 1-2 week post-procedure visit. | 
| Patient Global Impression of Improvement (PGI-I) score | Score on PGI-I at the patient's 1-2 week post-procedure visit. This score assesses who the patient feels their post-procedure condition is compared to prior to the procedure on a scale of 1-7, where 1 is very much better and 7 is very much worse. | 1-2 week post op visit | 
| Adverse events | apneic episodes > 15 seconds, patient lack of responsiveness, patient dissociative behavior, hypotension with blood pressure < 90/50, bradycardia < 50bpm, hypoxia with oxygen saturation <92% on pulse oximetry, significant nausea or vomiting | during the procedure | 
| Blood pressure | We will record blood pressure every 5 minutes during the procedure | during the procedure | 
| Episodes of hypoxia | We will record any oxygen saturation < 92% during the procedure | during the procedure | 
| Episodes of bradycardia | We will record any episodes of heart rate < 60bpm during the procedure | during the procedure | 
| Episodes of tachycardia | We will record episodes of heart rate > 100bpm during the procedure | during the procedure | 
| Patient's suspected group assignment | 10 minutes after the procedure, the patients will be asked to which treatment arm they suspected they were allocated | 10 minutes after the procedure |