Obstructive Sleep Apnea, Tonsillitis, Pain, Procedural
Conditions
Brief summary
The purpose of this study is to compare the use of short acting opioids (fentanyl/hydromorphone) with long acting opioids (methadone) for pain control following tonsillectomy surgery.
Detailed description
This is a single center, randomized, double blind, parallel-group dose escalation investigation which will compare post operative pain control indices for patients receiving short acting versus long acting opioids as intraoperative analgesics. Surgical and anesthesia care, except for intraoperative opioid management, are not altered for study purposes. Subjects are randomized 2:1 to either long-duration (methadone) or short-duration opioid (fentanyl, hydromorphone) through the perioperative period. Exploratory data will be collected for up to 30 days post-operatively.
Interventions
Per routine care
DRUGMethadone
Initial dosing 0.1mg/kg, potential to escalate to 0.15mg/kg following interim analysis
Sponsors
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
Yes
Inclusion criteria
* Children ages 3 to 17 years old * Presenting for elective tonsillectomy +/- adenoidectomy * Provide informed consent / assent (as appropriate)
Exclusion criteria
* History of liver or kidney disease * Females with positive pregnancy test * Severe sleep apnea (Sleep study with Apnea Hypopnea Index (AHI) \> 10) * Consistent daily opioid use for chronic pain ( \>3 months)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Amount of Opioid Medications Administered | Up to 7 days post surgery | Postoperative opioid medication expressed in oral morphine equivalents (OME) per kilogram |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Scores on the Parent Post Operative Pain Measure (PPPM) That Indicate Clinically Significant Pain | Up to 7 days post surgery | The PPPM has 15 yes/no questions which results in a score from 0-15, where a higher score indicates greater pain. A score of at least 6 out of 15 signifies clinically significant pain. The percentage of scores \> or = 6 is shown below. |
| NIH PROMIS (Patient-Reported Outcomes Measurement Information System) Parent Proxy Report Scale | Up to 7 days post surgery | Patient caregiver (as proxy) pain scores over past 7 days. Scale of 1 to 6, where 1=had no pain and 6=almost always had pain. |
| Evaluation of Participant's Pain as Measured by Numeric Pain Rating Scale | Up to 7 days post surgery | Numeric Pain Rating Scale has a range of 0 to 10, where 0=no pain and 10=worst possible pain. |
| Doses of Prescription Opioid Used Following Hospital Discharge | Up to 7 days post surgery | Number of doses of prescription medication used. |
| Opioid Administration in the PACU (Post-anesthesia Care Unit) | Up to 6 hours post surgery | Opioid medication use in the recovery room expressed in oral morphine equivalents (OME) per kilogram. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Short Acting Opioids: Fentanyl, Hydromorphone Fentanyl/Hydromorphone: Per routine care | 20 |
| Long Acting Opioid: Methadone 0.1mg/kg Low dose methadone: 0.1mg/kg | 20 |
| Long Acting Opioid: Methadone 0.15mg/kg High dose methadone: 0.15mg/kg | 20 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 2 | 2 |
Baseline characteristics
| Characteristic | Short Acting Opioids: Fentanyl, Hydromorphone | Total | Long Acting Opioid: Methadone 0.15mg/kg | Long Acting Opioid: Methadone 0.1mg/kg |
|---|---|---|---|---|
| Age, Continuous | 4.0 years | 4.3 years | 4.5 years | 4.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 8 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 52 Participants | 17 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 10 Participants | 6 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 6 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 41 Participants | 12 Participants | 18 Participants |
| Region of Enrollment United States | 20 Participants | 60 Participants | 20 Participants | 20 Participants |
| Sex: Female, Male Female | 7 Participants | 30 Participants | 9 Participants | 14 Participants |
| Sex: Female, Male Male | 13 Participants | 30 Participants | 11 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 22 | 0 / 23 |
| other Total, other adverse events | 0 / 21 | 0 / 22 | 0 / 23 |
| serious Total, serious adverse events | 1 / 21 | 0 / 22 | 0 / 23 |
Outcome results
Primary
Total Amount of Opioid Medications Administered
Postoperative opioid medication expressed in oral morphine equivalents (OME) per kilogram
Time frame: Up to 7 days post surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Short Acting Opioids: Fentanyl, Hydromorphone | Total Amount of Opioid Medications Administered | 1.5 morphine mg equivalents/kg |
| Long Acting Opioid: Methadone (0.1mg/kg) | Total Amount of Opioid Medications Administered | 0.9 morphine mg equivalents/kg |
| Long Acting Opioid: Methadone (0.15mg/kg) | Total Amount of Opioid Medications Administered | 0.5 morphine mg equivalents/kg |
p-value: 0.045Kruskal-Wallis
p-value: 0.023Kruskal-Wallis
Secondary
Doses of Prescription Opioid Used Following Hospital Discharge
Number of doses of prescription medication used.
Time frame: Up to 7 days post surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Short Acting Opioids: Fentanyl, Hydromorphone | Doses of Prescription Opioid Used Following Hospital Discharge | 4 doses |
| Long Acting Opioid: Methadone (0.1mg/kg) | Doses of Prescription Opioid Used Following Hospital Discharge | 2 doses |
| Long Acting Opioid: Methadone (0.15mg/kg) | Doses of Prescription Opioid Used Following Hospital Discharge | 3 doses |
p-value: 0.144Kruskal-Wallis
p-value: 0.322Kruskal-Wallis
Secondary
Evaluation of Participant's Pain as Measured by Numeric Pain Rating Scale
Numeric Pain Rating Scale has a range of 0 to 10, where 0=no pain and 10=worst possible pain.
Time frame: Up to 7 days post surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Short Acting Opioids: Fentanyl, Hydromorphone | Evaluation of Participant's Pain as Measured by Numeric Pain Rating Scale | 4.0 score on a scale | Standard Deviation 2.5 |
| Long Acting Opioid: Methadone (0.1mg/kg) | Evaluation of Participant's Pain as Measured by Numeric Pain Rating Scale | 3.7 score on a scale | Standard Deviation 1.9 |
| Long Acting Opioid: Methadone (0.15mg/kg) | Evaluation of Participant's Pain as Measured by Numeric Pain Rating Scale | 3.8 score on a scale | Standard Deviation 2.3 |
Secondary
NIH PROMIS (Patient-Reported Outcomes Measurement Information System) Parent Proxy Report Scale
Patient caregiver (as proxy) pain scores over past 7 days. Scale of 1 to 6, where 1=had no pain and 6=almost always had pain.
Time frame: Up to 7 days post surgery
Population: Participants who were less than 13 years of age.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Short Acting Opioids: Fentanyl, Hydromorphone | NIH PROMIS (Patient-Reported Outcomes Measurement Information System) Parent Proxy Report Scale | 2.4 score on a scale | Standard Deviation 1.5 |
| Long Acting Opioid: Methadone (0.1mg/kg) | NIH PROMIS (Patient-Reported Outcomes Measurement Information System) Parent Proxy Report Scale | 2.2 score on a scale | Standard Deviation 1.2 |
| Long Acting Opioid: Methadone (0.15mg/kg) | NIH PROMIS (Patient-Reported Outcomes Measurement Information System) Parent Proxy Report Scale | 2.3 score on a scale | Standard Deviation 1.1 |
Secondary
Opioid Administration in the PACU (Post-anesthesia Care Unit)
Opioid medication use in the recovery room expressed in oral morphine equivalents (OME) per kilogram.
Time frame: Up to 6 hours post surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Short Acting Opioids: Fentanyl, Hydromorphone | Opioid Administration in the PACU (Post-anesthesia Care Unit) | 0.15 morphine mg equivalents/kg |
| Long Acting Opioid: Methadone (0.1mg/kg) | Opioid Administration in the PACU (Post-anesthesia Care Unit) | 0.04 morphine mg equivalents/kg |
| Long Acting Opioid: Methadone (0.15mg/kg) | Opioid Administration in the PACU (Post-anesthesia Care Unit) | 0 morphine mg equivalents/kg |
p-value: 0.061Kruskal-Wallis
p-value: 0.021Kruskal-Wallis
Secondary
Percentage of Scores on the Parent Post Operative Pain Measure (PPPM) That Indicate Clinically Significant Pain
The PPPM has 15 yes/no questions which results in a score from 0-15, where a higher score indicates greater pain. A score of at least 6 out of 15 signifies clinically significant pain. The percentage of scores \> or = 6 is shown below.
Time frame: Up to 7 days post surgery
Population: Participants who were less than 13 years of age. Each participant reported 7 scores.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Short Acting Opioids: Fentanyl, Hydromorphone | Percentage of Scores on the Parent Post Operative Pain Measure (PPPM) That Indicate Clinically Significant Pain | 57 percentage of PPPM scores |
| Long Acting Opioid: Methadone (0.1mg/kg) | Percentage of Scores on the Parent Post Operative Pain Measure (PPPM) That Indicate Clinically Significant Pain | 61 percentage of PPPM scores |
| Long Acting Opioid: Methadone (0.15mg/kg) | Percentage of Scores on the Parent Post Operative Pain Measure (PPPM) That Indicate Clinically Significant Pain | 63 percentage of PPPM scores |