Compare Fentanyl Nasal Spray With Intravenous Opioids to Treat Severe Pain

Study Overview
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Brief Summary
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The goal of this clinical research study is to compare fentanyl nasal spray with a standard drug given by vein (hydromorphone hydrochloride) to help reduce pain related to cancer in patients coming to the emergency department.

Detailed Description
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Study Groups and Drug Administration: If participant agrees to take part in this study, they will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups. This is done because no one knows if one study group is better, the same, or worse than the other group. Participant will have an equal chance of being in either group: If participant is in Group 1, they will receive the fentanyl nasal spray. The study staff will help participant use the nasal spray. If participant is in Group 2, the emergency center nurse will give them the hydromorphone hydrochloride by vein. Study Procedures: Participant will stay in the emergency department for at least 4 hours and will be monitored after receiving fentanyl or hydromorphone hydrochloride. During this time, participant will be asked about their pain and any side effects they may be having every 15 minutes for 2 hours and then every 30 minutes for another 2 hours. The study staff will also monitor participant's vital signs, and ask them a few more questions at the end of the study. Length of Study Participation: Although participant will stay in the emergency department for at least 4 hours, the average length of stay for participants with severe pain is about 9 hours. When participant is discharged from the emergency department or admitted to the hospital, their active participation in the study is over. Follow-Up Phone Call: About 24 hours after patient's active participation is over, the study nurse will call them to ask if they had any other side effects since taking part in the study. The phone call should last about 5 minutes. If participant is still an inpatient at the hospital, the study nurse may visit them and ask them these questions in person. This is an investigational study. Hydromorphone hydrochloride is FDA approved and commercially available for the treatment of pain. Fentanyl nasal spray is FDA approved and commercially available for the treatment of pain. Its use to help with cancer pain in the emergency department is investigational. Up to 84 participants will be enrolled in this study. All will take part at MD Anderson.

Official Title
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A Randomized Trial to Compare Fentanyl Nasal Spray With Intravenous Opioids to Treat Severe Pain in Cancer Patients in the Emergency Department Setting

Conditions
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Advanced Cancers, Pain

Intervention / Treatment
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* Drug: Fentanyl Nasal Spray
* Drug: Hydromorphone Hydrochloride
* Behavioral: Phone Call


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cancer patients with severe pain (i.e., >=7 on NRS, see Table 1) already on opioid therapy for one week or longer, at least 60 mg of oral morphine/day, 25 mcg of transdermal fentanyl/hour, 30 mg of oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day, or an equianalgesic dose of another opioid. Ability to give informed consent before any trial-related activities (Trial-related activities are any procedure that would not have been performed during normal management of the subject.) Ability and willingness to communicate the intensity of pain using NRS at the frequency dictated by the protocol Exclusion Criteria: Patients with a history of chronic active hepatitis, cirrhosis or hepatic encephalopathy Inability to give informed consent Known or suspected hypersensitivity or intolerance to fentanyl or hydromorphone or excipients in the study medications Patients with sinusitis, obstruction of nasal passages, nasopharyngeal cancer, paranasal sinus malignancies, or any conditions in the nasopharyngeal anatomical area that may affect the absorption of fentanyl nasal spray. Females who are pregnant, breast-feeding or intending to become pregnant. This exclusion criterion will be assessed by questioning the patient about the pregnancy status, breast-feeding status, the intent to become pregnant, the menopausal status, and the date of the last menstrual period. Females of child-bearing potential, who are not using adequate contraceptive measures (including condoms, birth control pills, intrauterine devices, contraceptive implants, or other US FDA-approved contraceptives) Previous participation in randomization in this trial Has taken oral immediate release opioids within 4 hours prior to arrival.
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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fentanyl Nasal Spray<br>Fentanyl nasal spray 100 mcg delivered at time 0 (defined as the time when intranasal Fentanyl spray is administered) with a rescue dose allowed at time 0.5 hour (h). Study nurse to call patient 24 hours after participation to ask about side effects since taking part in the study. | Drug: Fentanyl Nasal Spray<br>* Fentanyl nasal spray 100 mcg delivered at time 0 (defined as the time when intranasal Fentanyl spray is administered) with a rescue dose allowed at time 0.5 hour (h)<br>Behavioral: Phone Call<br>* Study nurse to call patient 24 hours after participation to ask about side effects since taking part in the study. The phone call should last about 5 minutes.<br>|
| Active Comparator: Hydromorphone Hydrochloride<br>Hydromorphone hydrochloride 1.5 mg pushed intravenously (IV) at time 0 (defined as the time of completion of opioid IV push) with a rescue dose allowed at time 0.5 hour (h). Study nurse to call patient 24 hours after participation to ask about side effects since taking part in the study. | Drug: Hydromorphone Hydrochloride<br>* Hydromorphone hydrochloride 1.5 mg pushed intravenously (IV) at time 0 (defined as the time of completion of opioid IV push) with a rescue dose allowed at time 0.5 hour (h).<br>Behavioral: Phone Call<br>* Study nurse to call patient 24 hours after participation to ask about side effects since taking part in the study. The phone call should last about 5 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-inferiority of Fentanyl Nasal Spray Versus Intravenous Opioids in the Change in the Numeric Rating Scale (NRS) Pain Intensity Score at One Hour, Starting From the Time of Drug Delivery (Treatment Initiation). | The median change in Numeric Rating Scale (NRS) pain intensity scores (assessed on an 11-point Likert scale with 0 = no pain and 10 = worst pain) from randomization, estimate of treatment initiation, to one hour post-treatment calculated for both treatment arms. | Baseline, One hour post time of drug delivery/treatment initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Change in Numeric Rating Scale (NRS) Pain Intensity Score | Change in NRS pain intensity scores from randomization to one hour after treatment start based on the percentage of participants with severe pain, NRS score = 7-10, one hour after treatment start for both treatment arms. Numeric Rating Scale (NRS) pain intensity scores (assessed on an 11-point Likert scale with 0 = no pain and 10 = worst pain). | One (1) hour after treatment start. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Cancers, Pain, Fentanyl nasal spray, Hydromorphone hydrochloride, Phone call, Numeric Rating Scale, NRS