Compare Fentanyl Nasal Spray With Intravenous Opioids to Treat Severe Pain
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Fentanyl Nasal Spray 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
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)
Behavioral: Phone Call
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.
|
| Active Comparator: Hydromorphone Hydrochloride 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
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).
Behavioral: Phone Call
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.
|
Outcome Measures
Primary Outcome Measures
- 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). [Baseline, One hour post 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.
Secondary Outcome Measures
- Number of Participants With Change in Numeric Rating Scale (NRS) Pain Intensity Score [One (1) hour after treatment start.]
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).
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
Investigators
- Principal Investigator: Sai-Ching J. Yeung, MD, PHD, M.D. Anderson Cancer Center
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- 2015-0086
- NCI-2015-01509
Study Results
Participant Flow
| Recruitment Details | Cancer patients presenting to the M. D. Anderson Cancer Center Emergency Department for treatment of acute breakthrough pain, who met study inclusion criteria. |
|---|---|
| Pre-assignment Detail | One (1) participant withdrew consent before treatment and 1 participant was found ineligible due to abnormal EKG. |
| Arm/Group Title | Treatment Arm 1 (Intranasal Fentanyl) | Treatment Arm 2 (Intravenous Hydromorphone) | No Medication Administered |
|---|---|---|---|
| Arm/Group Description | Fentanyl Nasal Spray 100mcg 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). | Hydromorphone Hydrochloride 1.5mg 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). | 1 Participant decided not to participate after signing the consent form; 1 Participant was found to have abnormal EKG changes with hypokalemia, hence removed from the study. |
| Period Title: Overall Study | |||
| STARTED | 42 | 40 | 2 |
| COMPLETED | 42 | 40 | 0 |
| NOT COMPLETED | 0 | 0 | 2 |
Baseline Characteristics
| Arm/Group Title | Treatment Arm 1 (Intranasal Fentanyl) | Treatment Arm 2 (Intravenous Hydromorphone) | No Medication Administered | Total |
|---|---|---|---|---|
| Arm/Group Description | Fentanyl Nasal Spray 100mcg 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). | Hydromorphone Hydrochloride 1.5mg 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). | 1 Participant decided not to participate after signing the consent form; 1 Participant was found to have abnormal EKG changes with hypokalemia, hence removed from the study. | Total of all reporting groups |
| Overall Participants | 42 | 40 | 2 | 84 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
35
83.3%
|
39
97.5%
|
2
100%
|
76
90.5%
|
| >=65 years |
7
16.7%
|
1
2.5%
|
0
0%
|
8
9.5%
|
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
54.21
(14.452)
|
50.33
(11.669)
|
46
(1.000)
|
52.32
(13.233)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
23
54.8%
|
23
57.5%
|
1
50%
|
47
56%
|
| Male |
19
45.2%
|
17
42.5%
|
1
50%
|
37
44%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
11
26.2%
|
6
15%
|
0
0%
|
17
20.2%
|
| Not Hispanic or Latino |
31
73.8%
|
34
85%
|
2
100%
|
67
79.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
1
2.4%
|
2
5%
|
0
0%
|
3
3.6%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
10
23.8%
|
3
7.5%
|
1
50%
|
14
16.7%
|
| White |
31
73.8%
|
35
87.5%
|
1
50%
|
67
79.8%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
42
100%
|
40
100%
|
2
100%
|
84
100%
|
| Baseline NRS Pain Intensity (NRS Pain Score) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [NRS Pain Score] |
8.69
(1.093)
|
8.95
(1.108)
|
NA
(NA)
|
8.82
(1.101)
|
Outcome Measures
| Title | 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). |
|---|---|
| Description | 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. |
| Time Frame | Baseline, One hour post time of drug delivery/treatment initiation |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment Arm 1 (Intranasal Fentanyl) | Treatment Arm 2 (Intravenous Hydromorphone) |
|---|---|---|
| Arm/Group Description | Fentanyl Nasal Spray 100mcg 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). | Hydromorphone Hydrochloride 1.5mg 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). |
| Measure Participants | 42 | 40 |
| Median (Standard Deviation) [NRS Pain Intensity Score] |
5.14
(2.16)
|
4.90
(2.31)
|
| Title | Number of Participants With Change in Numeric Rating Scale (NRS) Pain Intensity Score |
|---|---|
| Description | 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). |
| Time Frame | One (1) hour after treatment start. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment Arm 1 (Intranasal Fentanyl) | Treatment Arm 2 (Intravenous Hydromorphone) |
|---|---|---|
| Arm/Group Description | Fentanyl Nasal Spray 100mcg 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). | Hydromorphone Hydrochloride 1.5mg 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). |
| Measure Participants | 42 | 40 |
| Count of Participants [Participants] |
5
11.9%
|
10
25%
|
Adverse Events
| Time Frame | Within 24 hours after ED discharge or hospital admission | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | No adverse events were reported prior to ED discharge or hospital admission. | |||||
| Arm/Group Title | Treatment Arm 1 (Intranasal Fentanyl) | Treatment Arm 2 (Intravenous Hydromorphone) | No Medication Administered | |||
| Arm/Group Description | Fentanyl Nasal Spray 100mcg 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). | Hydromorphone Hydrochloride 1.5mg 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). | 1 Participant decided not to participate after signing the consent form; 1 Participant was found to have abnormal EKG changes with hypokalemia, hence removed from the study. | |||
All Cause Mortality |
||||||
| Treatment Arm 1 (Intranasal Fentanyl) | Treatment Arm 2 (Intravenous Hydromorphone) | No Medication Administered | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/42 (0%) | 0/40 (0%) | 0/2 (0%) | |||
Serious Adverse Events |
||||||
| Treatment Arm 1 (Intranasal Fentanyl) | Treatment Arm 2 (Intravenous Hydromorphone) | No Medication Administered | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/42 (0%) | 0/40 (0%) | 0/2 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Treatment Arm 1 (Intranasal Fentanyl) | Treatment Arm 2 (Intravenous Hydromorphone) | No Medication Administered | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/42 (2.4%) | 3/40 (7.5%) | 0/2 (0%) | |||
| Gastrointestinal disorders | ||||||
| Nausea | 0/42 (0%) | 1/40 (2.5%) | 0/2 (0%) | |||
| General disorders | ||||||
| Fatigue | 0/42 (0%) | 2/40 (5%) | 0/2 (0%) | |||
| Nervous system disorders | ||||||
| Headache | 1/42 (2.4%) | 3/40 (7.5%) | 0/2 (0%) | |||
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Sai-Ching J. Yeung, MD, Professor, Emergency Medicine |
|---|---|
| Organization | UT MD Anderson Cancer Center |
| Phone | (713) 745-9911 |
| syeung@mdanderson.org |
- 2015-0086
- NCI-2015-01509