Anemia, Sickle Cell, Pain
Conditions
Keywords
fentanyl, intranasal, sickle cell, vasoocclusive crisis, pain crisis, pediatrics
Brief summary
The purpose of this study is to determine if intranasal fentanyl can decrease the pain of patients with sickle cell disease who present to the pediatric emergency department with a vaso-occlusive crisis.
Detailed description
Principles of therapy for treatment of vaso-occlusive crises include early aggressive analgesic therapy with opiates and non-steroidal anti-inflammatory agents as well as fluid administration. It is known that there is a significant delay in time to administration of analgesics in children with VOC in the ED. The most easily modifiable factor that contributes to delayed opiate administration is route of administration. Intranasal medication administration is an easy, rapid way to administer opiates with minimal discomfort as well as bypassing first past metabolism and the blood brain barrier. Intranasal fentanyl has been shown to be a safe and effective analgesic for treatment of acute pain in children, reaching therapeutic effect in 2-10 minutes after administration. The investigators believe that intranasal fentanyl therapy will be able to provide expedited and effective pain therapy to patients with sickle cell disease presenting to the pediatric emergency department with a vaso-occlusive crisis
Interventions
DRUGFentanyl Citrate
A single dose of fentanyl citrate (2 mcg/kg; max 100mcg) administered intranasally. Half of the volume will be administered in each nare. The medication will be administered using a mucosal atomization device
DRUGNormal Saline
A single dose of equivalent volume of 0.9% Normal Saline will be administered intranasally. Half of the volume will be administered in each nare. The medication will be administered using a mucosal atomization device.
Sponsors
Montefiore Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Sickle Cell Disease * Ages 3 years - 21 years
Exclusion criteria
for Enrollment: * Pregnancy * Known allergy to Fentanyl * Usage of daily home opiates
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pain Score 20 Minutes After Administration of Study Drug | Baseline and 20 minutes after administration of study drug | Change in pain score between 0 and 20 minutes using the Wong Baker FACES pain scale (WBFPS). The WBFPRS has six faces, with each face representing an increasing severity of pain the more rightward it is on the scale (0 is the lowest score , which represents the least amount of pain, while 10 is the highest score which represents the greatest level of pain).. Each face has an even number underneath it, consecutively. To calculate the change, the reported pain score at 20 minutes was subtracted from the reported baseline pain score. Thus, the higher change in pain score is indicative of a GREATER change in pain (i.e. greater decrease in pain at 20 minutes compared to baseline). The greatest possible changes in pain would be a 10 (pain score of 10 at baseline and 0 at 20 minutes) representing a DECREASE in pain between the two time points, and -10 (pain score of 0 at baseline and 10 at 20 minutes) representing a INCREASE in pain between the two time points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Presence of Headache | Participants will be followed for the duration of their ED visit, an expected average of 6 hours | — |
| Admission Rate | This will be assessed at either discharge from the ED or admission to an inpatient unit, an expected average of 6 hours after triage | — |
| Length of Stay in ED | Time from triage until either discharge from the ED or admission to an inpatient unit, an expected average of 6 hours | Given multiple confounding factors, reliable data was not able to be obtained for this outcome measure |
| Total Amount of Narcotics Administered | Participants will be followed for the duration of their ED visit, an expected average of 6 hours | Given multiple confounding and extraneous factors, reliable data was not able to be obtained for this outcome measure |
| Time to Study Drug Administration | Time from triage to adminstration of study drug | — |
| Presence of Bradycardia | Every 5 minutes until 30 minutes after study drug administration | Number of participants who had bradycardia |
| Change in Pain Score at 30 Minutes | Baseline and 30 minutes after administration of study drug | Change in pain score between 0 and 30 minutes using the Wong Baker FACES pain scale (WBFPS). The WBFPRS has six faces, with each face representing an increasing severity of pain the more rightward it is on the scale (0 is the lowest score, which represents the least amount of pain, while 10 is the highest score which represents the greatest level of pain).. Each face has an even number underneath it, consecutively. To calculate the change, the reported pain score at 30 minutes was subtracted from the reported baseline pain score. Thus, the higher change in pain score is indicative of a GREATER change in pain (i.e. greater decrease in pain at 30 minutes compared to baseline). The greatest possible changes in pain would be a 10 (pain score of 10 at baseline and 0 at 30 minutes) representing a DECREASE in pain between the two time points, and -10 (pain score of 0 at baseline and 10 at 30 minutes) representing a INCREASE in pain between the two time points. |
| Change in Pain Score | Baseline and immediately prior to IV insertion | Due to confounding factors we were unable to obtain reliable data for this outcome |
| Respiratory Distress | Every 5 minutes until 30 minutes after study drug administration | Participants who had respiratory distress within 30 min of study drug administration |
| Hypotension | Every 5 minutes until 30 minutes after study drug administration | Participants who had hypotension within 30 min of study drug administration |
| Hypoxia | Every 5 minutes until 30 minutes after study drug administration | Number of participants who had hypoxia within 30 min of study drug adminsitration |
| Change in Pain Score at 10 Minutes | Baseline and 10 minutes after administration of study drug | Change in pain score between 0 and 10 minutes using the Wong Baker FACES pain scale (WBFPS). The WBFPRS has six faces, with each face representing an increasing severity of pain the more rightward it is on the scale (0 is the lowest score , which represents the least amount of pain, while 10 is the highest score which represents the greatest level of pain).. Each face has an even number underneath it, consecutively. To calculate the change, the reported pain score at 10 minutes was subtracted from the reported baseline pain score. Thus, the higher change in pain score is indicative of a GREATER change in pain (i.e. greater decrease in pain at 10 minutes compared to baseline). The greatest possible changes in pain would be a 10 (pain score of 10 at baseline and 0 at 10 minutes) representing a DECREASE in pain between the two time points, and -10 (pain score of 0 at baseline and 10 at 10 minutes) representing a INCREASE in pain between the two time points. |
Countries
United States
Participant flow
Recruitment details
Subjects were PRE-CONSENTED for the study in the outpatient hematology clinic, inpatient floors prior to discharge or a separate emergency department (ED) visit prior to discharge. This was done to prevent decision making while under emotional duress of a vaso-occlusive crisis (VOC). PRE-CONSENT occurred from 12.12.2011-1.8.2015
Pre-assignment details
124 subjects were consented for the study. The study drug was only administered one time in the ED if subjects met all inclusion and exclusion criteria when they arrived with a VOC. Only 49 of the 124 consented subjects received the study drug.
Participants by arm
| Arm | Count |
|---|---|
| Intranasal Saline Normal Saline: A single dose of equivalent volume of 0.9% Normal Saline will be administered intranasally. Half of the volume will be administered in each nare. The medication will be administered using a mucosal atomization device. | 25 |
| Intranasal Fentnayl Fentanyl Citrate: A single dose of fentanyl citrate (2 mcg/kg; max 100mcg) administered intranasally. Half of the volume will be administered in each nare. The medication will be administered using a mucosal atomization device | 24 |
| Total | 49 |
Baseline characteristics
| Characteristic | Intranasal Saline | Intranasal Fentnayl | Total |
|---|---|---|---|
| Age, Continuous | 12.5 years STANDARD_DEVIATION 5.1 | 10.6 years STANDARD_DEVIATION 5.3 | 11.6 years STANDARD_DEVIATION 5.2 |
| Duration of VOC 1/2-1day | 5 participants | 7 participants | 12 participants |
| Duration of VOC <1/2 day | 7 participants | 9 participants | 16 participants |
| Duration of VOC 1-2 day | 6 participants | 4 participants | 10 participants |
| Duration of VOC >2 day | 7 participants | 4 participants | 11 participants |
| Location of VOC Abdomen | 6 participants | 10 participants | 16 participants |
| Location of VOC Arms | 5 participants | 9 participants | 14 participants |
| Location of VOC Back | 12 participants | 12 participants | 24 participants |
| Location of VOC Chest | 4 participants | 7 participants | 11 participants |
| Location of VOC Head | 1 participants | 4 participants | 5 participants |
| Location of VOC Legs | 12 participants | 10 participants | 22 participants |
| Oral analgesic within 2h prior to study drug | 2 participants | 3 participants | 5 participants |
| Sex: Female, Male Female | 6 Participants | 13 Participants | 19 Participants |
| Sex: Female, Male Male | 19 Participants | 11 Participants | 30 Participants |
| Type of Sickle Cell Disease SB | 0 participants | 1 participants | 1 participants |
| Type of Sickle Cell Disease SC | 6 participants | 3 participants | 9 participants |
| Type of Sickle Cell Disease SS | 19 participants | 20 participants | 39 participants |
| weight | 45 kg | 28 kg | 37 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 25 | 12 / 24 |
| serious Total, serious adverse events | 2 / 25 | 5 / 24 |
Outcome results
Primary
Change in Pain Score 20 Minutes After Administration of Study Drug
Change in pain score between 0 and 20 minutes using the Wong Baker FACES pain scale (WBFPS). The WBFPRS has six faces, with each face representing an increasing severity of pain the more rightward it is on the scale (0 is the lowest score , which represents the least amount of pain, while 10 is the highest score which represents the greatest level of pain).. Each face has an even number underneath it, consecutively. To calculate the change, the reported pain score at 20 minutes was subtracted from the reported baseline pain score. Thus, the higher change in pain score is indicative of a GREATER change in pain (i.e. greater decrease in pain at 20 minutes compared to baseline). The greatest possible changes in pain would be a 10 (pain score of 10 at baseline and 0 at 20 minutes) representing a DECREASE in pain between the two time points, and -10 (pain score of 0 at baseline and 10 at 20 minutes) representing a INCREASE in pain between the two time points.
Time frame: Baseline and 20 minutes after administration of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intranasal Saline | Change in Pain Score 20 Minutes After Administration of Study Drug | 1 units on a scale |
| Intranasal Fentnayl | Change in Pain Score 20 Minutes After Administration of Study Drug | 2 units on a scale |
p-value: 0.048Wilcoxon (Mann-Whitney)
Secondary
Admission Rate
Time frame: This will be assessed at either discharge from the ED or admission to an inpatient unit, an expected average of 6 hours after triage
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intranasal Saline | Admission Rate | 16 participants |
| Intranasal Fentnayl | Admission Rate | 13 participants |
p-value: >0.05Chi-squared
Secondary
Change in Pain Score
Due to confounding factors we were unable to obtain reliable data for this outcome
Time frame: Baseline and immediately prior to IV insertion
Secondary
Change in Pain Score at 10 Minutes
Change in pain score between 0 and 10 minutes using the Wong Baker FACES pain scale (WBFPS). The WBFPRS has six faces, with each face representing an increasing severity of pain the more rightward it is on the scale (0 is the lowest score , which represents the least amount of pain, while 10 is the highest score which represents the greatest level of pain).. Each face has an even number underneath it, consecutively. To calculate the change, the reported pain score at 10 minutes was subtracted from the reported baseline pain score. Thus, the higher change in pain score is indicative of a GREATER change in pain (i.e. greater decrease in pain at 10 minutes compared to baseline). The greatest possible changes in pain would be a 10 (pain score of 10 at baseline and 0 at 10 minutes) representing a DECREASE in pain between the two time points, and -10 (pain score of 0 at baseline and 10 at 10 minutes) representing a INCREASE in pain between the two time points.
Time frame: Baseline and 10 minutes after administration of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intranasal Saline | Change in Pain Score at 10 Minutes | 0 units on a scale |
| Intranasal Fentnayl | Change in Pain Score at 10 Minutes | 2 units on a scale |
p-value: >0.05Wilcoxon (Mann-Whitney)
Secondary
Change in Pain Score at 30 Minutes
Change in pain score between 0 and 30 minutes using the Wong Baker FACES pain scale (WBFPS). The WBFPRS has six faces, with each face representing an increasing severity of pain the more rightward it is on the scale (0 is the lowest score, which represents the least amount of pain, while 10 is the highest score which represents the greatest level of pain).. Each face has an even number underneath it, consecutively. To calculate the change, the reported pain score at 30 minutes was subtracted from the reported baseline pain score. Thus, the higher change in pain score is indicative of a GREATER change in pain (i.e. greater decrease in pain at 30 minutes compared to baseline). The greatest possible changes in pain would be a 10 (pain score of 10 at baseline and 0 at 30 minutes) representing a DECREASE in pain between the two time points, and -10 (pain score of 0 at baseline and 10 at 30 minutes) representing a INCREASE in pain between the two time points.
Time frame: Baseline and 30 minutes after administration of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intranasal Saline | Change in Pain Score at 30 Minutes | 2 units on a scale |
| Intranasal Fentnayl | Change in Pain Score at 30 Minutes | 2 units on a scale |
p-value: >0.05Wilcoxon (Mann-Whitney)
Secondary
Hypotension
Participants who had hypotension within 30 min of study drug administration
Time frame: Every 5 minutes until 30 minutes after study drug administration
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intranasal Saline | Hypotension | 2 participants |
| Intranasal Fentnayl | Hypotension | 2 participants |
Secondary
Hypoxia
Number of participants who had hypoxia within 30 min of study drug adminsitration
Time frame: Every 5 minutes until 30 minutes after study drug administration
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intranasal Saline | Hypoxia | 0 participants |
| Intranasal Fentnayl | Hypoxia | 3 participants |
p-value: >0.05Fisher Exact
Secondary
Length of Stay in ED
Given multiple confounding factors, reliable data was not able to be obtained for this outcome measure
Time frame: Time from triage until either discharge from the ED or admission to an inpatient unit, an expected average of 6 hours
Secondary
Presence of Bradycardia
Number of participants who had bradycardia
Time frame: Every 5 minutes until 30 minutes after study drug administration
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intranasal Saline | Presence of Bradycardia | 0 participants |
| Intranasal Fentnayl | Presence of Bradycardia | 0 participants |
Secondary
Presence of Headache
Time frame: Participants will be followed for the duration of their ED visit, an expected average of 6 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intranasal Saline | Presence of Headache | 0 participants |
| Intranasal Fentnayl | Presence of Headache | 4 participants |
p-value: =0.05Fisher Exact
Secondary
Respiratory Distress
Participants who had respiratory distress within 30 min of study drug administration
Time frame: Every 5 minutes until 30 minutes after study drug administration
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intranasal Saline | Respiratory Distress | 0 participants |
| Intranasal Fentnayl | Respiratory Distress | 0 participants |
Secondary
Time to Study Drug Administration
Time frame: Time from triage to adminstration of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intranasal Saline | Time to Study Drug Administration | 47 minutes | Standard Deviation 28 |
| Intranasal Fentnayl | Time to Study Drug Administration | 43 minutes | Standard Deviation 36 |
p-value: =0.68t-test, 2 sided
Secondary
Total Amount of Narcotics Administered
Given multiple confounding and extraneous factors, reliable data was not able to be obtained for this outcome measure
Time frame: Participants will be followed for the duration of their ED visit, an expected average of 6 hours