Opioid-use Disorder
Conditions
Brief summary
There is limited guidance on the optimal management of buprenorphine perioperatively and both buprenorphine discontinuation and continuation are acceptable standards of care. Buprenorphine continuation at low analgesic dosing is also accepted, however is not provided as a potential treatment strategy by the Substance Abuse and Mental Health Services Administration (SAMHSA). There is the risk of inadequate pain control necessitating opioid escalation when buprenorphine is continued. Preliminary clinical observations support buprenorphine continuation at low analgesic doses (8mg) as it adequately facilitates postoperative pain management without interrupting opioid use disorder (OUD) treatment, however to date, no prospective trial has investigated this treatment strategy in comparison to full dose buprenorphine continuation. Since optimal perioperative dosing strategies remain unknown, the purpose of this study is to investigate if buprenorphine continuation at analgesic dosing is superior to full dose buprenorphine continuation in individuals presenting for elective surgery.
Detailed description
The purpose of this study is to investigate whether buprenorphine continuation at analgesic dosing is superior to full dose buprenorphine continuation in individuals presenting for elective surgery. Adults scheduled for elective surgery who are taking ≥12mg buprenorphine for OUD treatment will be eligible for this study. Enrolled participants will be randomized to receive either a reduced analgesic dose of buprenorphine (8mg) or to continue buprenorphine on the day of surgery without dose reduction. The primary outcome of interest is postoperative pain scores. The secondary outcomes of interest are opioid consumption, opioid dispensing up to 30 days following the surgical procedure and OUD related symptoms, including opioid withdrawal, cravings and relapse. The investigators hypothesis is that there will be a clinically significant increase in pain scores when buprenorphine is continued in full compared to when it is continued at a lower analgesic dose. Clinical significance will be defined as a difference in composite pain scores of greater than 20% between groups. The investigators also hypothesize that opioid consumption and opioid dispensing will be greater with full dose buprenorphine continuation compared to low-dose continuation.
Interventions
DRUGBuprenorphine
Patients randomized to this group will reduce their buprenorphine dose prior to surgery.
Sponsors
National Institute of General Medical Sciences (NIGMS)
MaineHealth
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* age 18 and older * American Society of Anesthesia health class I-III * Currently taking buprenorphine formulation equivalent to 12mg or greater for at least 30 days for treatment of Opioid Use Disorder * Scheduled for surgery at Maine Medical Center for a procedure with a greater than 4/10 pain intensity is expected on post-op day one.
Exclusion criteria
* unable to consent to the study * currently pregnant * current major medical illness that could limit the ability to utilize medications within our protocol driven multimodal analgesic plan (e.g. cancer, severe end-stage organ disease, or dementia)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-operative Pain Scores: 24 Hours After Surgery | 24 hours after surgery | Highest, average, and lowest pain scores will be evaluated using the Numerical Rating Scale of 0 (no pain) -10 (worst pain) |
| Post-operative Pain Scores: 48 Hours After Surgery | 48 hours after surgery | Highest, average, and lowest pain scores will be evaluated using the Numerical Rating Scale of 0 (no pain) -10 (worst pain) |
| Post-operative Pain Scores: 72 Hours After Surgery | 72 hours after surgery | Highest, average, and lowest pain scores will be evaluated using the Numerical Rating Scale of 0 (no pain) -10 (worst pain) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Opioid Cravings | 1-3 hours prior to surgery | Measured by the Opioid Craving Scale (OCS); scale ranges from 0-30 with higher scores indicating higher levels of cravings |
| Opioid Consumption | 3 days post-op | All opioids consumed through 72 hours after surgery combined into mean morphine equivalents |
| Opioid Relapse | 30 days following surgery | Patient reported use of non-prescribed opioids |
| Opioid Misuse | 1-3 hours prior to surgery | Measured by the Current Opioid Misuse Measure ((COMM); scores can range from 0-68, scores of 9 or lower indicates a low risk of opioid misuse or abuse, scores higher than 9 indicate a high risk) |
| Opioid Dispensing | 30 days following surgery | Prescriptions filled for the patient in the Prescription Awareness Tool |
| Opioid Withdrawal | 1-3 hours prior to surgery | Withdrawal symptoms as measured by the Clinical Opioid Withdrawal Scale (COWS, scores can range from 0-48 \[5-12 mild; 13-24, moderate; 25-36, moderately severe; \>36, severe withdrawal) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Buprenorphine Dose Reduction Patients instructed to reduce buprenorphine to 8mg prior to surgery
Buprenorphine: Patients randomized to this group will reduce their buprenorphine dose prior to surgery. | 6 |
| Buprenorphine Full Dose Continuation Patients instructed to continue taking the full prescribed dose of buprenorphine.
Buprenorphine: Patients randomized to this group will continue their buprenorphine at the full prescribed dose. | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Buprenorphine Dose Reduction | Buprenorphine Full Dose Continuation | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 12 Participants |
| Age, Continuous | 40.6 years STANDARD_DEVIATION 5.3 | 40.5 years STANDARD_DEVIATION 5.7 | 40.6 years STANDARD_DEVIATION 50.3 |
| Current buprenorphine dose | 15 mg | 16 mg | 16 mg |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 6 Participants | 5 Participants | 11 Participants |
| Region of Enrollment United States | 6 participants | 6 participants | 12 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Post-operative Pain Scores: 24 Hours After Surgery
Highest, average, and lowest pain scores will be evaluated using the Numerical Rating Scale of 0 (no pain) -10 (worst pain)
Time frame: 24 hours after surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Buprenorphine Dose Reduction | Post-operative Pain Scores: 24 Hours After Surgery | Average | 7.2 score on a scale (NRS pain scale) | Standard Deviation 1.5 |
| Buprenorphine Dose Reduction | Post-operative Pain Scores: 24 Hours After Surgery | Lowest | 6.0 score on a scale (NRS pain scale) | Standard Deviation 2.4 |
| Buprenorphine Dose Reduction | Post-operative Pain Scores: 24 Hours After Surgery | Highest | 8.3 score on a scale (NRS pain scale) | Standard Deviation 1.4 |
| Buprenorphine Full Dose Continuation | Post-operative Pain Scores: 24 Hours After Surgery | Average | 5.8 score on a scale (NRS pain scale) | Standard Deviation 2.4 |
| Buprenorphine Full Dose Continuation | Post-operative Pain Scores: 24 Hours After Surgery | Lowest | 4.5 score on a scale (NRS pain scale) | Standard Deviation 2.7 |
| Buprenorphine Full Dose Continuation | Post-operative Pain Scores: 24 Hours After Surgery | Highest | 7.4 score on a scale (NRS pain scale) | Standard Deviation 2.8 |
Primary
Post-operative Pain Scores: 48 Hours After Surgery
Highest, average, and lowest pain scores will be evaluated using the Numerical Rating Scale of 0 (no pain) -10 (worst pain)
Time frame: 48 hours after surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Buprenorphine Dose Reduction | Post-operative Pain Scores: 48 Hours After Surgery | Average | 6.8 score on a scale (NRS) | Standard Deviation 2.5 |
| Buprenorphine Dose Reduction | Post-operative Pain Scores: 48 Hours After Surgery | Lowest | 6.2 score on a scale (NRS) | Standard Deviation 2.5 |
| Buprenorphine Dose Reduction | Post-operative Pain Scores: 48 Hours After Surgery | Highest | 7.8 score on a scale (NRS) | Standard Deviation 2.3 |
| Buprenorphine Full Dose Continuation | Post-operative Pain Scores: 48 Hours After Surgery | Average | 5.4 score on a scale (NRS) | Standard Deviation 1.6 |
| Buprenorphine Full Dose Continuation | Post-operative Pain Scores: 48 Hours After Surgery | Lowest | 2.8 score on a scale (NRS) | Standard Deviation 0.8 |
| Buprenorphine Full Dose Continuation | Post-operative Pain Scores: 48 Hours After Surgery | Highest | 7.7 score on a scale (NRS) | Standard Deviation 2.1 |
Primary
Post-operative Pain Scores: 72 Hours After Surgery
Highest, average, and lowest pain scores will be evaluated using the Numerical Rating Scale of 0 (no pain) -10 (worst pain)
Time frame: 72 hours after surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Buprenorphine Dose Reduction | Post-operative Pain Scores: 72 Hours After Surgery | Average | 6.6 score on a scale (NRS) | Standard Deviation 1.6 |
| Buprenorphine Dose Reduction | Post-operative Pain Scores: 72 Hours After Surgery | Lowest | 5.2 score on a scale (NRS) | Standard Deviation 1.6 |
| Buprenorphine Dose Reduction | Post-operative Pain Scores: 72 Hours After Surgery | Highest | 7.4 score on a scale (NRS) | Standard Deviation 1.9 |
| Buprenorphine Full Dose Continuation | Post-operative Pain Scores: 72 Hours After Surgery | Average | 5.1 score on a scale (NRS) | Standard Deviation 2.3 |
| Buprenorphine Full Dose Continuation | Post-operative Pain Scores: 72 Hours After Surgery | Lowest | 4.1 score on a scale (NRS) | Standard Deviation 2.5 |
| Buprenorphine Full Dose Continuation | Post-operative Pain Scores: 72 Hours After Surgery | Highest | 6.1 score on a scale (NRS) | Standard Deviation 2.4 |
Secondary
Opioid Consumption
All opioids consumed through 72 hours after surgery combined into mean morphine equivalents
Time frame: 3 days post-op
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Buprenorphine Dose Reduction | Opioid Consumption | 37.25 morphine milligram equivalents (MME) |
| Buprenorphine Full Dose Continuation | Opioid Consumption | 41.43 morphine milligram equivalents (MME) |
Secondary
Opioid Cravings
Measured by the Opioid Craving Scale (OCS); scale ranges from 0-30 with higher scores indicating higher levels of cravings
Time frame: 30 days following surgery
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Buprenorphine Dose Reduction | Opioid Cravings | 0.67 score on a scale |
| Buprenorphine Full Dose Continuation | Opioid Cravings | 3 score on a scale |
Secondary
Opioid Cravings
Measured by the Opioid Craving Scale (OCS); scale ranges from 0-30 with higher scores indicating higher levels of cravings
Time frame: 1-3 hours prior to surgery
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Buprenorphine Dose Reduction | Opioid Cravings | 2.17 score on a scale |
| Buprenorphine Full Dose Continuation | Opioid Cravings | 2 score on a scale |
Secondary
Opioid Dispensing
Prescriptions filled for the patient in the Prescription Awareness Tool
Time frame: 30 days following surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Buprenorphine Dose Reduction | Opioid Dispensing | 262 morphine milligram equivalents |
| Buprenorphine Full Dose Continuation | Opioid Dispensing | 308 morphine milligram equivalents |
Secondary
Opioid Misuse
Measured by the Current Opioid Misuse Measure ((COMM); scores can range from 0-68, scores of 9 or lower indicates a low risk of opioid misuse or abuse, scores higher than 9 indicate a high risk)
Time frame: 30 days following surgery
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Buprenorphine Dose Reduction | Opioid Misuse | 3.33 score on a scale (COMM) |
| Buprenorphine Full Dose Continuation | Opioid Misuse | 8 score on a scale (COMM) |
Secondary
Opioid Misuse
Measured by the Current Opioid Misuse Measure ((COMM); scores can range from 0-68, scores of 9 or lower indicates a low risk of opioid misuse or abuse, scores higher than 9 indicate a high risk)
Time frame: 1-3 hours prior to surgery
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Buprenorphine Dose Reduction | Opioid Misuse | 2.83 score on a scale (COMM) |
| Buprenorphine Full Dose Continuation | Opioid Misuse | 7 score on a scale (COMM) |
Secondary
Opioid Relapse
Patient reported use of non-prescribed opioids
Time frame: 30 days following surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Buprenorphine Dose Reduction | Opioid Relapse | 0 number of patients reporting relapse |
| Buprenorphine Full Dose Continuation | Opioid Relapse | 0 number of patients reporting relapse |
Secondary
Opioid Withdrawal
Withdrawal symptoms as measured by the Clinical Opioid Withdrawal Scale (COWS, scores can range from 0-48 \[5-12 mild; 13-24, moderate; 25-36, moderately severe; \>36, severe withdrawal)
Time frame: 1-3 hours prior to surgery
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Buprenorphine Dose Reduction | Opioid Withdrawal | less than 5 on the COWS scale | 5 Participants |
| Buprenorphine Dose Reduction | Opioid Withdrawal | 5-12 on the COWS scale, mild withdrawal | 1 Participants |
| Buprenorphine Full Dose Continuation | Opioid Withdrawal | less than 5 on the COWS scale | 5 Participants |
| Buprenorphine Full Dose Continuation | Opioid Withdrawal | 5-12 on the COWS scale, mild withdrawal | 1 Participants |