Intranasal Fentanyl as an Analgesic for Cystoscopic Procedures

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy of intranasally-administrated fentanyl spray to decrease the pain during cystoscopy (the passage of a telescopic instrument into the bladder for purpose of diagnosing the cause of blood in the urine, urinary complaints or any other problems with the urinary bladder). The current standard practice is to use Lidocaine jelly (a local anesthetic) given through the urethra to lubricate and decrease pain. In this study, an additional medicine (fentanyl) is used to reduce pain that occurs during and after the above procedure.

Detailed Description
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In this double-blind study, a nasal spray of either the drug (fentanyl -- an opioid analgesic) or placebo (normal saline) is administered before the procedure. There is a 50% chance that patients receive the drug or the placebo. In either case, local Lidocaine jelly is used as an anesthetic in the urethra. Each patient is compensated for time and traveling after the completion of his/her participation. Patients are asked to arrive between 7 and 11 PM on the evening prior to their procedure for an overnight admission to 5 East ward, on the 5th floor of the Harbor UCLA Medical Center in Torrance, California, United States. Once there, vital signs (blood pressure, pulse, oxygen saturation -- amount of oxygen in the blood, and breathing rate) is checked and an intravenous line is placed. Before, during and after the procedure, patients are asked to rate their pain on a scale of 0 to 10 with 0 being no pain and 10 being the worst pain possible. Regardless of whether patients are assigned to receive fentanyl or placebo, they receive the standard of care for this cystoscopic procedure. Once in the cystoscopy room, patients receive the study drug by nasal (into the nose) spray. The study drug is supplied in a pre-filled syringe that contains either 100 mcg of fentanyl or placebo (normal saline with no active medicine in it). Once the study drug is given, the vital signs are closely monitored(checked) until the effect of drug wears off, usually between 2 and 4 hours. Blood samples are drawn on several occasions. This blood is used to see how much of the study drug (fentanyl or placebo) appears in the blood. Adverse effects: The well-known adverse effects of opioids may occur after nasal as well as conventional routes of administration; however, severe adverse effects such as respiratory depression or hypotension do not seem to occur in any appreciable frequency. Intranasal fentanyl has been used safely and effectively in many studies. There are no reports of any serious side effects with the small dose (100 mcg) that is being used in this study. Intranasal fentanyl is generally well tolerated with no serious adverse events. In cancer patients treated for breakthrough pain, the main treatment related side effects were nausea, vertigo, dizziness, constipation, and somnolence. For local side effects, fentanyl displays little local irritation, nasal discomfort or taste experiences. Nasal irritation, skin pain, nasal mucosa ulcers and dysgeusia have been occasionally reported as minor side effects. The following minor side effects have been reported with other forms of fentanyl (oral, patch or intravenous): anxiety; confusion; difficulty walking; dizziness; drowsiness; dry mouth; headache; itching; nausea and vomiting. The following severe side effects have not been reported with intranasal fentanyl but have been reported with other forms of fentanyl (oral, patch or intravenous): allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); excessive dizziness; excessive drowsiness; fainting; fatigue; hallucinations; muscle rigidity; seizures; shock (changes in skin color); slow heartbeat; respiratory depression or slowed breathing; trouble breathing and feeling of weakness. Advantages to patients: If effective, less pain during and after the cystoscopic procedure and better tolerance of the procedure. Advantages to humanity: If effective, nasal fentanyl could be used as a means to reduce pain before and during cystoscopic procedures. These benefits may not happen and unexpected side effects may develop.

Official Title
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A Prospective, Randomized, Double Blind Study Comparing the Efficacy and Safety of Fentanyl Nasal Spray to Placebo as an Analgesic, in Patients Undergoing Outpatient Cystoscopic Procedures

Conditions
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Pain

Intervention / Treatment
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* Drug: Fentanyl
* Drug: saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Urological indications for cystoscopic procedure. Exclusion Criteria: History of analgesia abuse or former opioid addiction. Allergy to fentanyl. Acute/chronic nasal problems such as rhinitis or sinusitis. Positive urine pregnancy test / lactation. Acute bronchial asthma / upper airway obstruction. Presence of bradycardia or a history of seizures. Concomitant use of drugs that inhibit CYP3A4 (e.g., ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, nefazodone, amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, MAO inhibitors and verapamil) 0-10 NRS pain score more than 3 on baseline. Any situation or condition which, in the investigator's opinion, puts the subject at significant risk, or could confound the study results.

Ages Eligible for Study
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Minimum Age: 18 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fentanyl<br>Subjects will receive either 0.5mL or 1 mL of intranasal fentanyl (50mcg or 100mcg) | Drug: Fentanyl<br>* 100 mcg in 1 mL intranasal spray<br>* Other names: fentanyl citrate;|
| Placebo Comparator: Placebo<br>Subjects will receive either 0.5mL or 1 mL of intranasal saline as placebo. | Drug: saline<br>* Sodium Chloride 0.9% intranasal spray<br>* Other names: normal saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre Procedure 0 - 10 Pain Numerical Rating Scale | The NRS pain assessment (0 = no pain to 10 = worst possible pain) is recorded as outlined below: 1. baseline pain score at admission, when the subject checks in, 2 Upon entry of the cystoscope into the urethral meatus, 3. and thirty minutes after the cystoscopic procedure has been completed. | Pre procedure, During procedure, Post procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| O2 Saturation Post Drug Administration | After administration of the study drug, the subject is monitored (oxygen saturation), for any signs of respiratory depression or the presence of complications or side-effects including apnea or oxygen desaturation. | Baseline, 5 minutes 10 minutes and 30 minutes post drug-administration. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intranasal fentanyl, Cystoscopy