Opioid Use, Pain, Postoperative
Conditions
Brief summary
The overall goal of this research is to improve perioperative pain treatment, decrease post-operative opioid consumption, diminish opioid related side effects, and reduce postop opioid prescribing (and hence opportunity for diversion, abuse, addiction, and fatal overdose).
Detailed description
This protocol will test the innovative, paradigm-shifting hypothesis that anesthesia for outpatient surgery with long-duration opioids (methadone), compared with conventional short-duration opioids, achieves better analgesia, with similar or diminished side effects, may reduce development of chronic postsurgical pain, improves recovery, and importantly, decreases postoperative opioid consumption and could hence diminish take-home opioid prescribing and shrink the population reservoir of unused opioids available for diversion and misuse. Two cohorts will be studied, but analyzed separately. 1) Short-stay, anticipated next-day discharge surgery (compare short-duration vs long-duration opioid), 2) Same-day discharge surgery (compare short-duration vs long-duration opioid).
Interventions
DRUGMethadone
Dose is 0.15-0.3 mg/kg IV methadone HCl given intraoperatively and in the immediate post-operative period. Intraoperative methadone doses are 15 mg in short-stay, anticipated next-day discharge patients (10 mg if ≤55kg), and 10 mg in same-day surgery patients.
DRUGFentanyl
Given per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)).
DRUGHydromorphone
Given per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)).
DRUGMorphine
Given per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)).
DRUGSufentanil
Given per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)).
Sponsors
National Institute on Drug Abuse (NIDA)
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-65 years Undergoing general anesthesia and moderately painful ambulatory surgery with anticipated postop stay of \< 24 hours * Signed, written, informed consent
Exclusion criteria
* History of liver or kidney disease. * Females who are pregnant or nursing. * Chronic opioid use (e.g. preoperative daily use of methadone, fentanyl transdermal patches, or ≥ 3 oxycodone pills)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total 30 Day Post-discharge Home Opioid Use (Number of Tablets) | Approximately 30 days | Based on home diary and hospital record. Number of opioid tablets from PACU discharge to postoperative day (POD) 30 for Same Day subjects, and number of opioid tablets from POD 1 to POD 30 for Short-Stay subjects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Intraoperative Non-methadone Opioid Administration | Approximately 12 hours | Based on hospital record. |
| Total Post Anesthesia Care Unit (PACU) Opioid Administration | Approximately 2 hours | Based on hospital record. |
| Total Hospital Non-methadone Opioid Administration | Start of surgery to hospital discharge, up to 2 days | Based on hospital record. |
| Total 7-day Post-PACU Discharge Home Opioid Use | Up to 7 days post-PACU discharge | Based on home diary and hospital record. Number of opioid tablets from PACU discharge to postoperative day (POD) 7 for Same Day subjects, and number of opioid tablets from POD 1 to POD 7 for Short-Stay subjects. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Short-stay, IV Methadone Anticipated next-day discharge; intraoperative and post-operative IV methadone
Methadone: Dose is 0.15-0.3 mg/kg IV methadone HCl given intraoperatively and in the immediate post-operative period. Intraoperative methadone doses are 15 mg in short-stay, anticipated next-day discharge patients (10 mg if ≤55kg), and 10 mg in same-day surgery patients. | 175 |
| Short-stay, IV Short-acting Opioids Anticipated next-day discharge; intraoperative and post-operative IV fentanyl, sufentanil, morphine, or hydromorphone at anesthesia provider discretion
Fentanyl: Given per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)).
Hydromorphone: Given per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)).
Morphine: Given per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)).
Sufentanil: Given per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)). | 175 |
| Same-day, IV Methadone Intraoperative and post-operative IV methadone
Methadone: Dose is 0.15-0.3 mg/kg IV methadone HCl given intraoperatively and in the immediate post-operative period. Intraoperative methadone doses are 15 mg in short-stay, anticipated next-day discharge patients (10 mg if ≤55kg), and 10 mg in same-day surgery patients. | 190 |
| Same-day, IV Short-acting Opioids Intraoperative and post-operative IV fentanyl, sufentanil, morphine or hydromorphone at anesthesia provider discretion
Fentanyl: Given per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)).
Hydromorphone: Given per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)).
Morphine: Given per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)).
Sufentanil: Given per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)). | 194 |
| Total | 734 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Physician Decision | 2 | 8 | 6 | 3 |
| Overall Study | Withdrawal by Subject | 11 | 5 | 9 | 8 |
Baseline characteristics
| Characteristic | Short-stay, IV Methadone | Total | Same-day, IV Short-acting Opioids | Same-day, IV Methadone | Short-stay, IV Short-acting Opioids |
|---|---|---|---|---|---|
| Age, Continuous | 41.8 years STANDARD_DEVIATION 13.4 | 43.0 years STANDARD_DEVIATION 12.8 | 43.6 years STANDARD_DEVIATION 12 | 44.6 years STANDARD_DEVIATION 12.3 | 41.6 years STANDARD_DEVIATION 13.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 25 Participants | 8 Participants | 7 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 161 Participants | 669 Participants | 173 Participants | 171 Participants | 164 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants | 40 Participants | 13 Participants | 12 Participants | 7 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants | 8 Participants | 2 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Asian | 2 Participants | 12 Participants | 5 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Black or African American | 39 Participants | 122 Participants | 18 Participants | 35 Participants | 30 Participants |
| Race/Ethnicity, Customized Race More than one race | 2 Participants | 7 Participants | 1 Participants | 4 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 2 Participants | 9 Participants | 1 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Unknown or Not Reported | 6 Participants | 17 Participants | 3 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Race White | 124 Participants | 559 Participants | 164 Participants | 140 Participants | 131 Participants |
| Region of Enrollment United States | 175 Participants | 734 Participants | 194 Participants | 190 Participants | 175 Participants |
| Sex: Female, Male Female | 84 Participants | 477 Participants | 142 Participants | 154 Participants | 97 Participants |
| Sex: Female, Male Male | 91 Participants | 257 Participants | 52 Participants | 36 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 188 | 1 / 188 | 0 / 205 | 0 / 205 |
| other Total, other adverse events | 21 / 188 | 17 / 188 | 29 / 205 | 16 / 205 |
| serious Total, serious adverse events | 6 / 188 | 6 / 188 | 10 / 205 | 11 / 205 |
Outcome results
Primary
Total 30 Day Post-discharge Home Opioid Use (Number of Tablets)
Based on home diary and hospital record. Number of opioid tablets from PACU discharge to postoperative day (POD) 30 for Same Day subjects, and number of opioid tablets from POD 1 to POD 30 for Short-Stay subjects.
Time frame: Approximately 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Short-stay, IV Methadone | Total 30 Day Post-discharge Home Opioid Use (Number of Tablets) | 10.00 tablets | Standard Deviation 15.5 |
| Short-stay, IV Short-acting Opioids | Total 30 Day Post-discharge Home Opioid Use (Number of Tablets) | 10.00 tablets | Standard Deviation 11.6 |
| Same-day, IV Methadone | Total 30 Day Post-discharge Home Opioid Use (Number of Tablets) | 6.18 tablets | Standard Deviation 8.4 |
| Same-day, IV Short-acting Opioids | Total 30 Day Post-discharge Home Opioid Use (Number of Tablets) | 6.67 tablets | Standard Deviation 10.4 |
p-value: 0.97Negative binomial regression
p-value: 0.631Negative binomial regression
Secondary
Total 7-day Post-PACU Discharge Home Opioid Use
Based on home diary and hospital record. Number of opioid tablets from PACU discharge to postoperative day (POD) 7 for Same Day subjects, and number of opioid tablets from POD 1 to POD 7 for Short-Stay subjects.
Time frame: Up to 7 days post-PACU discharge
Population: Participants with data collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Short-stay, IV Methadone | Total 7-day Post-PACU Discharge Home Opioid Use | 6.50 tablets | Standard Deviation 8.1 |
| Short-stay, IV Short-acting Opioids | Total 7-day Post-PACU Discharge Home Opioid Use | 8.20 tablets | Standard Deviation 8.7 |
| Same-day, IV Methadone | Total 7-day Post-PACU Discharge Home Opioid Use | 4.96 tablets | Standard Deviation 5.8 |
| Same-day, IV Short-acting Opioids | Total 7-day Post-PACU Discharge Home Opioid Use | 5.45 tablets | Standard Deviation 7.2 |
p-value: 0.105Negative binomial regression
p-value: 0.531Negative binomial regression
Secondary
Total Hospital Non-methadone Opioid Administration
Based on hospital record.
Time frame: Start of surgery to hospital discharge, up to 2 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Short-stay, IV Methadone | Total Hospital Non-methadone Opioid Administration | 30 Milligram Morphine Equivalent (MME) |
| Short-stay, IV Short-acting Opioids | Total Hospital Non-methadone Opioid Administration | 128 Milligram Morphine Equivalent (MME) |
| Same-day, IV Methadone | Total Hospital Non-methadone Opioid Administration | 0 Milligram Morphine Equivalent (MME) |
| Same-day, IV Short-acting Opioids | Total Hospital Non-methadone Opioid Administration | 68 Milligram Morphine Equivalent (MME) |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Total Intraoperative Non-methadone Opioid Administration
Based on hospital record.
Time frame: Approximately 12 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Short-stay, IV Methadone | Total Intraoperative Non-methadone Opioid Administration | 0.0 Milligram Morphine Equivalent (MME) |
| Short-stay, IV Short-acting Opioids | Total Intraoperative Non-methadone Opioid Administration | 18.0 Milligram Morphine Equivalent (MME) |
| Same-day, IV Methadone | Total Intraoperative Non-methadone Opioid Administration | 0.0 Milligram Morphine Equivalent (MME) |
| Same-day, IV Short-acting Opioids | Total Intraoperative Non-methadone Opioid Administration | 16.7 Milligram Morphine Equivalent (MME) |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Total Post Anesthesia Care Unit (PACU) Opioid Administration
Based on hospital record.
Time frame: Approximately 2 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Short-stay, IV Methadone | Total Post Anesthesia Care Unit (PACU) Opioid Administration | 2.0 Milligram Morphine Equivalent (MME) |
| Short-stay, IV Short-acting Opioids | Total Post Anesthesia Care Unit (PACU) Opioid Administration | 3.0 Milligram Morphine Equivalent (MME) |
| Same-day, IV Methadone | Total Post Anesthesia Care Unit (PACU) Opioid Administration | 2.0 Milligram Morphine Equivalent (MME) |
| Same-day, IV Short-acting Opioids | Total Post Anesthesia Care Unit (PACU) Opioid Administration | 2.5 Milligram Morphine Equivalent (MME) |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: 0.004Wilcoxon (Mann-Whitney)