Pain
Conditions
Keywords
analgesia,, buprenorphine, clonidine, dexamethasone, bupivacaine, nerve block
Brief summary
After total joint replacement, early hospital discharge to home (with patients capable of continuing a home-based rehabilitation program) is a cost- effective management strategy. This project will use improved local anesthetic nerve block techniques to enhance technical capability and clinical practice by (i) reducing pain and other morbidities during recovery, (ii) improving weight-bearing achievement during in-hospital physical therapy to allow for earlier return home, and (iii) continued rehabilitation as an outpatient at home when feasible (versus in an extended care facility).
Detailed description
Patients will have spinal anesthesia for their hip or knee replacement surgery. They will also receive the nerve blocks described above
Interventions
DRUGBupivacaine + CBD (clonidine, buprenorphine, dexamethasone)
Nerve blocks before surgery of L2-L4 and L4-S3 for Knee replacements Nerve blocks before surgery of L2-L4 for hip replacements
DRUGBupivacaine Only (control arm)
Nerve blocks before surgery of L2-L4 and L4-S3 for Knee replacements Nerve blocks before surgery of L2-L4 for hip replacements
Sponsors
University of Pittsburgh
Brian Williams
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Age between 18 and 85, and undergoing a total knee or hip replacement. 2. Fluent in English, decision competent, willing and able to provide written informed consent, and able to complete the study's schedule of assessments. 3. Able to walk \>3m without an assisting device. 4. Have a BMI ≤ 40 kg/m2.
Exclusion criteria
1. Current participation in another orthopedic/Physical Therapy/rehab/anesthesiology interventional clinical trial. 2. Are at significant behavioral risks or have refractory major psychiatric disorders. 3. Revision surgery on the same extremity. 4. Have an American Surgical Association (ASA) Physical Status classification of 4 or higher. 5. Have been diagnosed with clinically significant neuropathy with its origins in either diabetes or other causes; have neuromuscular disease that would influence data collection. 6. Have a surgically-fused lumbar spine, or a spinal cord simulator, or other condition that would contraindicate or prohibit the conduct of spinal anesthesia. 7. At significant risk for postoperative substance abuse, or immediate-postoperative substance abuse withdrawal symptoms (alcohol, cocaine, enrolled in methadone or buprenorphine opioid withdrawal programs, etc.) Previous or current use of marijuana will not be an exclusion for study enrollment. 8. Are undergoing Total Knee Arthroplasty (TKA)/Total Hip Arthroplasty (THA) for a tumor. 9. Have contraindications (e.g., anaphylaxis) to any of the study drugs. 10. Have a systemic fungal infection. 11. Have a known hypersensitivity to bupivacaine hydrochloride or to any local anesthetic of the amide-type or to other components of bupivacaine hydrochloride solutions. 12. Have a known or suspected buprenorphine hypersensitivity (not including nausea and/or vomiting). 13. Have a gastro-intestinal (GI) obstruction. 14. Have paralytic ileus. 15. Pregnant women 16. Have had a kidney or liver transplant. Veterans will not be excluded from participation based on smoking status, diagnosis of obstructive sleep apnea, or baseline monitored consumption of therapeutic opioids for documented medical indications; instead, these variables will be codified and quantified for subsequent covariate statistical analysis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Short-Form McGill Pain Questionnaire (Version 2) Total Score Difference From Baseline | Baseline, Post-Operative day after surgery (7AM-9AM EST) | SF-MPQ version 2 total score difference of Post-Operative Day 1 value minus the Baseline value. Differences can range from -10 to +10. Negative scores indicate a decrease in pain. |
| SF-MPQ2 Continuous Pain Subscore Difference From Baseline | Baseline, Post-Operative day after surgery (7AM-9AM EST) | Continuous pain subscore difference of Post-Operative Day 1 value minus the Baseline value. Differences can range from -10 to +10. Negative scores indicate a decrease in pain. |
| SF-MPQ2 Intermittent Pain Subscore Difference From Baseline | Baseline, Post-Operative day after surgery (7AM-9AM EST) | Intermittent pain subscore difference of Post-Operative Day 1 value minus the Baseline value. Differences can range from -10 to +10. Negative scores indicate a decrease in pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Recovery 15 Item Scale (QoR-15) Total Score | Day after surgery (7AM-9AM EST) | Quality of Recovery 15 Item Scale, total score 0-150, 150 reflecting a perfect score and better recovery. |
| Performed-based Physical Function is Assessed Using the Repeated Chair Stand Test. | 6 weeks post-operation | The Repeated Chair Stand Test is a timed test based on the ability of the participant to perform a series of standing exercises. This test is germane to subjects with total joint replacement that are easily performed in the clinical settings. The test will capture the domains of muscle strength and activation, and balance. |
| Performed-based Physical Function is Assessed Using the Standing Balance Test. | 6 weeks post-operation | The Standing Balance Test score based on the ability of the participant to perform a series of standing exercises. Scores range from 0 to 4, with 4 indicating a longer time holding the stand (a better outcome). This test is germane to subjects with total joint replacement that are easily performed in the clinical settings. The test will capture the domains of muscle strength and activation, and balance. |
| Performed-based Physical Function is Assessed Using the Self-Selected Gait Speed Test. | 6 weeks post-operation | The Self-Selected Gait Speed Test is a timed test based on the ability of the participant to walk a 4 meter distance. This test is germane to subjects with total joint replacement that are easily performed in the clinical settings. The test captures the ability to walk. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled from November 2016 to October 2018 after HIPAA-compliant contact of the study recruiter by either the preoperative clinic or the orthopedic clinic clinical staff. Of the 571 screened, 473 were not eligible due to failing study inclusion/exclusion criteria (N=151), programmatic reasons (N=145), or not willing to participate (N=177), resulting in 98 patients enrolled in the study. Twenty of these were early terminations, leaving 78.
Pre-assignment details
Study temporarily on-hold (6), Failed screening (3), Failed spinal (2), No study staff available (2), Surgery deferred (2), Current participation in another clinical trial (1), Intra-operative peri-prosthetic fracture (1), Patient chose another hospital (1), Surgery cancelled due to profuse vomiting after spinal anesthesia (1), and Uni-compartmental knee arthroplasty instead of total knee (1).
Participants by arm
| Arm | Count |
|---|---|
| Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone) Patients will receive a nerve blocks consisting of bupivacaine plus buprenorphine-clonidine-dexamethasone (Bupivacaine-BCD)
Bupivacaine + BCD (buprenorphine, clonidine, dexamethasone): Nerve blocks before surgery of L2-L4 and L4-S3 for Knee and Hip replacements. | 62 |
| Bupivacaine Only (Control Arm) Patients will receive a nerve block consisting of bupivacaine only.
Bupivacaine Only (control arm): Nerve blocks before surgery of L2-L4 and L4-S3 for Knee and Hip replacements. | 16 |
| Total | 78 |
Baseline characteristics
| Characteristic | Bupivacaine Only (Control Arm) | Total | Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone) |
|---|---|---|---|
| Age, Continuous | 65.6 years STANDARD_DEVIATION 7.6 | 66 years STANDARD_DEVIATION 7.5 | 66.7 years STANDARD_DEVIATION 7.4 |
| BMI (kg/m^2) | 31.9 kg/m^2 STANDARD_DEVIATION 5.1 | 32 kg/m^2 STANDARD_DEVIATION 5 | 32.6 kg/m^2 STANDARD_DEVIATION 4.6 |
| Diabetes | 6 participants | 29 participants | 23 participants |
| Race/Ethnicity, Customized African American | 1 Participants | 9 Participants | 8 Participants |
| Race/Ethnicity, Customized Caucasian | 15 Participants | 68 Participants | 53 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 16 Participants | 78 Participants | 62 Participants |
| Sex: Female, Male Female | 3 Participants | 9 Participants | 6 Participants |
| Sex: Female, Male Male | 13 Participants | 69 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 62 | 0 / 16 |
| other Total, other adverse events | 1 / 62 | 0 / 16 |
| serious Total, serious adverse events | 0 / 62 | 0 / 16 |
Outcome results
Primary
SF-MPQ2 Continuous Pain Subscore Difference From Baseline
Continuous pain subscore difference of Post-Operative Day 1 value minus the Baseline value. Differences can range from -10 to +10. Negative scores indicate a decrease in pain.
Time frame: Baseline, Post-Operative day after surgery (7AM-9AM EST)
Population: All participants who completed the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone) | SF-MPQ2 Continuous Pain Subscore Difference From Baseline | -2.29 units on a scale | Standard Deviation 2.43 |
| Bupivacaine Only (Control Arm) | SF-MPQ2 Continuous Pain Subscore Difference From Baseline | 0.33 units on a scale | Standard Deviation 2.76 |
Comparison: Comparison of SF-MPQ2 Continuous Pain Subscore Difference From Baseline between the 4-drug nerve block group and the bupivacaine only groupp-value: 0.001t-test, 2 sided
Primary
SF-MPQ2 Intermittent Pain Subscore Difference From Baseline
Intermittent pain subscore difference of Post-Operative Day 1 value minus the Baseline value. Differences can range from -10 to +10. Negative scores indicate a decrease in pain.
Time frame: Baseline, Post-Operative day after surgery (7AM-9AM EST)
Population: All participants who completed the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone) | SF-MPQ2 Intermittent Pain Subscore Difference From Baseline | -2.79 units on a scale | Standard Deviation 2.66 |
| Bupivacaine Only (Control Arm) | SF-MPQ2 Intermittent Pain Subscore Difference From Baseline | -1.14 units on a scale | Standard Deviation 3.27 |
Comparison: Comparison of SF-MPQ2 Intermittent Pain Subscore Difference From Baseline between the 4-drug nerve block group and the bupivacaine only groupp-value: 0.038t-test, 2 sided
Primary
Short-Form McGill Pain Questionnaire (Version 2) Total Score Difference From Baseline
SF-MPQ version 2 total score difference of Post-Operative Day 1 value minus the Baseline value. Differences can range from -10 to +10. Negative scores indicate a decrease in pain.
Time frame: Baseline, Post-Operative day after surgery (7AM-9AM EST)
Population: All participants who completed the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone) | Short-Form McGill Pain Questionnaire (Version 2) Total Score Difference From Baseline | -1.85 score on a scale | Standard Deviation 2.04 |
| Bupivacaine Only (Control Arm) | Short-Form McGill Pain Questionnaire (Version 2) Total Score Difference From Baseline | -0.05 score on a scale | Standard Deviation 2.38 |
Comparison: Comparison of SF-MPQ2 Total Score Difference From Baseline between the 4-drug nerve block group and the bupivacaine only groupp-value: 0.003t-test, 2 sided
Secondary
Performed-based Physical Function is Assessed Using the Repeated Chair Stand Test.
The Repeated Chair Stand Test is a timed test based on the ability of the participant to perform a series of standing exercises. This test is germane to subjects with total joint replacement that are easily performed in the clinical settings. The test will capture the domains of muscle strength and activation, and balance.
Time frame: 6 weeks post-operation
Population: All participants who completed the protocol. There was missing data for five participants in the Bupivacaine + BCD arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone) | Performed-based Physical Function is Assessed Using the Repeated Chair Stand Test. | 12.34 seconds | Standard Deviation 4.31 |
| Bupivacaine Only (Control Arm) | Performed-based Physical Function is Assessed Using the Repeated Chair Stand Test. | 11.93 seconds | Standard Deviation 2.09 |
Comparison: Comparison of Repeated Chair Stand time at 6 week post-procedure between the 4-drug nerve block group and the bupivacaine only group.p-value: 0.711t-test, 2 sided
Secondary
Performed-based Physical Function is Assessed Using the Self-Selected Gait Speed Test.
The Self-Selected Gait Speed Test is a timed test based on the ability of the participant to walk a 4 meter distance. This test is germane to subjects with total joint replacement that are easily performed in the clinical settings. The test captures the ability to walk.
Time frame: 6 weeks post-operation
Population: All of the participants who completed the protocol. There was missing data for four participants in the Bupivacaine + BCD arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone) | Performed-based Physical Function is Assessed Using the Self-Selected Gait Speed Test. | 0.88 meters per second | Standard Deviation 0.2 |
| Bupivacaine Only (Control Arm) | Performed-based Physical Function is Assessed Using the Self-Selected Gait Speed Test. | 0.94 meters per second | Standard Deviation 0.21 |
Comparison: Comparison of Self-Selected Gait Speed rate at 6 week post-procedure between the 4-drug nerve block group and the bupivacaine only group.p-value: 0.339t-test, 2 sided
Secondary
Performed-based Physical Function is Assessed Using the Standing Balance Test.
The Standing Balance Test score based on the ability of the participant to perform a series of standing exercises. Scores range from 0 to 4, with 4 indicating a longer time holding the stand (a better outcome). This test is germane to subjects with total joint replacement that are easily performed in the clinical settings. The test will capture the domains of muscle strength and activation, and balance.
Time frame: 6 weeks post-operation
Population: All participants who completed the protocol. There was missing data for four participants in the Bupivacaine + BCD arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone) | Performed-based Physical Function is Assessed Using the Standing Balance Test. | 3.86 score on a scale | Standard Deviation 0.44 |
| Bupivacaine Only (Control Arm) | Performed-based Physical Function is Assessed Using the Standing Balance Test. | 3.94 score on a scale | Standard Deviation 0.25 |
Comparison: Comparison of Standing Balance Test score at 6 week post-procedure between the 4-drug nerve block group and the bupivacaine only groupp-value: 0.512t-test, 2 sided
Secondary
Quality of Recovery 15 Item Scale (QoR-15) Total Score
Quality of Recovery 15 Item Scale, total score 0-150, 150 reflecting a perfect score and better recovery.
Time frame: 6 weeks post-operation
Population: All participants who completed the protocol. There was missing data for one participant in the Bupivacaine + BCD arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone) | Quality of Recovery 15 Item Scale (QoR-15) Total Score | 128.89 score on a scale | Standard Deviation 24.26 |
| Bupivacaine Only (Control Arm) | Quality of Recovery 15 Item Scale (QoR-15) Total Score | 130.06 score on a scale | Standard Deviation 21.75 |
Comparison: Comparison of QoR-15 Total Score at 6 week post-procedure between the 4-drug nerve block group and the bupivacaine only groupp-value: 0.861t-test, 2 sided
Secondary
Quality of Recovery 15 Item Scale (QoR-15) Total Score
Quality of Recovery 15 Item Scale, total score 0-150, 150 reflecting a perfect score and better recovery.
Time frame: Day after surgery (7AM-9AM EST)
Population: All participants who completed the protocol. There was missing data for one participant in the Bupivacaine Only arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone) | Quality of Recovery 15 Item Scale (QoR-15) Total Score | 106.08 score on a scale | Standard Deviation 19.76 |
| Bupivacaine Only (Control Arm) | Quality of Recovery 15 Item Scale (QoR-15) Total Score | 90.13 score on a scale | Standard Deviation 24.15 |
Comparison: Comparison of QoR-15 Total Score at post-operative day 1 between the 4-drug nerve block group and the bupivacaine only groupp-value: 0.009t-test, 2 sided