Fentanyl for Breakthrough Pain in the Emergency Department

Study Overview
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Brief Summary
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The goal of this clinical research study is to learn if fentanyl nasal spray can help decrease pain related to cancer when used with other drugs for pain. Researchers also want to know if this drug can help decrease the length of your stay in the Emergency Department. In this study, fentanyl nasal spray will be compared to a placebo nasal spray. A placebo is not a drug. It looks like the study drug but it is not designed to treat any disease or illness. It is designed in this study to be compared with the study spray to learn if the study spray has any real effect. You will also be given intravenous (IV) pain drugs. You will be given these drugs even if you decide not to take part in this study.

Detailed Description
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Study Groups: If you agree to take part in this study, you will be randomly assigned (as in the flip of a coin) to receive either fentanyl nasal spray or a placebo nasal spray. You will have an equal chance of being assigned to either group. Neither you nor the study staff will know if you are receiving the study spray or the placebo. However, if needed for your safety, the study staff will be able to find out what you are receiving. Study Visit and Study Treatment: During your stay in the Emergency Department today, the following tests and procedures will be performed: Your vital signs (blood pressure, heart rate, temperature, and breathing rate) will be recorded. Information from your medical record about your age, sex, race, status of the disease, and any drugs that you may be taking for pain. The study nurse will also ask you some questions about your pain. It should take about 5 minutes to answer these questions. You will then begin study treatment with either the fentanyl nasal spray or placebo nasal spray. The study nurse will help you use the nasal spray. You will stay in the Emergency Department and will be monitored for up to 8 hours after the treatment has been administered. During this time, you will be asked about your pain and any side effects you may be having. The study nurse will also monitor your IV pain drug levels and other vital signs. Length of Treatment: Your active participation in this study will be over after your are monitored for up to 8 hours, at which time you will either be discharged to go home or admitted to the hospital based on your pain response and any other health problems that may be found during your visit to the Emergency Department. Follow-Up Phone Call: About 24 hours after your participation is over, the study nurse will call you by phone to ask if you experienced any other side effects since finishing the study treatment. The phone call should only last about 5 minutes. If you are still an inpatient at the hospital, the study nurse may visit you and ask you these questions in person. This is an investigational study. Fentanyl nasal spray is FDA approved and commercially available for the treatment of pain. It's use to help with cancer pain in the Emergency Department is investigational. Up to 60 patients will take part in this study. All will be enrolled at MD Anderson.

Official Title
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A Randomized Controlled Double-Blind Trial of Fentanyl Nasal Spray (Lazanda) Plus Hydromorphone Demand PCA Versus Placebo Nasal Spray Plus Hydromorphone Demand PCA for Treatment of Breakthrough Cancer Pain in the Emergency Department

Conditions
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Pain

Intervention / Treatment
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* Drug: Fentanyl Nasal Spray
* Drug: Hydromorphone PCA
* Other: Placebo Nasal Spray


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cancer patients presenting to the Emergency Department for treatment of acute breakthrough pain who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain. (Patients considered opioid tolerant are those who are taking at least: 60 mg of oral morphine/day, 25 mcg of transdermal fentanyl/hour, 30 mg oral oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day, or an equianalgesic dose of another opioid for a week or longer.) Patients must have severe pain on an 11-point Numeric Rating Scale (NRS 7-10) Breakthrough cancer pain must be of sufficient severity to warrant the use of intravenous opioids in the judgment of the treating emergency physician Age between 18 and 75 years Able to understand the description of the study and give informed consent Patients must be willing to and capable of providing frequent pain assessments for up to 8 hours English-speaking Exclusion Criteria: Patients will not be approached while they are in acute distress and those exhibiting symptoms (such as dyspnea, uncontrolled nausea/vomiting or vertigo) to such an extent that impairs their ability to understand and evaluate informed consent Patients participating in other clinical trials for pain Patients who are not already tolerant to opioids Patients, who in the judgment of the treating clinician, are suspected to have hepatic or renal failure Patients who are pregnant or lactating Patients with a known allergy or significant reaction to fentanyl, the components of the IN formulation, hydromorphone, or other opioids Patients already on high morphine equivalent daily dose (MEDDs) (>500 mg/day).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fentanyl Nasal Spray + Hydromorphone PCA<br>Fentanyl 100 mcg nasal spray administered plus hydromorphone PCA. All study patients receive demand dosing patient-controlled analgesia (PCA) with intravenous hydromorphone. Initial loading dose 0.2 mg with demand doses of 0.2 mg and lockout interval of 15 minutes. There will be no basal dose and the 8-hour dose limit will be 6.4 mg. | Drug: Fentanyl Nasal Spray<br>* 100 mcg nasal spray administered in each nostril.<br>* Other names: Lazanda;Drug: Hydromorphone PCA<br>* Initial loading dose 0.2 mg with demand doses of 0.2 mg and lockout interval of 15 minutes. There will be no basal dose and the 8-hour dose limit will be 6.4 mg.<br>* Other names: Dilaudid;|
| Experimental: Placebo Nasal Spray + Hydromorphone PCA<br>Placebo nasal spray administered plus hydromorphone PCA . All study patients receive demand dosing patient-controlled analgesia (PCA) with intravenous hydromorphone. Initial loading dose 0.2 mg with demand doses of 0.2 mg and lockout interval of 15 minutes. There will be no basal dose and the 8-hour dose limit will be 6.4 mg. | Drug: Hydromorphone PCA<br>* Initial loading dose 0.2 mg with demand doses of 0.2 mg and lockout interval of 15 minutes. There will be no basal dose and the 8-hour dose limit will be 6.4 mg.<br>* Other names: Dilaudid;Other: Placebo Nasal Spray<br>* 1 placebo nasal spray administered in each nostril.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Total Pain Relief Score (TOTPAR4) at Four Hours After Treatment Initiation. | Primary outcome is total pain relief score (TOTPAR4) at 4 hours after treatment initiation. TOTPAR4 defined as the sum of hourly pain relief scores after baseline to four hours after the first administered dose of Lazanda or placebo. Scores range from -1 (worse pain) to 4 (complete relief). Range of possible TOTPAR4 summed scores is -4 to 16. A TOTPAR4 score greater than or equal to 8 is considered a positive response. | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Breakthrough cancer pain, Emergency Department, ED, Fentanyl nasal spray, Lazanda, Placebo nasal spray, Hydromorphone PCA, Dilaudid