4-drug Nerve Block Versus Plain Local Anesthetic for Knee and Hip Arthroplasty Analgesia in Veterans

• Sponsor: Brian Williams (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT02891798
• Collaborator: University of Pittsburgh (Other)
• Enrollment: 98
• Location: 1
• Arms: 2
• Duration (Months): 58.6
• Patients Per Site Per Month: 1.7

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Pain	Drug: Bupivacaine + CBD (clonidine, buprenorphine, dexamethasone); Drug: Bupivacaine Only (control arm)	Phase 3

Detailed Description

Patients will have spinal anesthesia for their hip or knee replacement surgery. They will also receive the nerve blocks described above

Study Design

• Study Type: Interventional
• Actual Enrollment: 98 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 4-drug Nerve Block Versus Plain Local Anesthetic for Knee and Hip Arthroplasty Analgesia in Veterans
• Study Start Date: Oct 1, 2016
• Actual Primary Completion Date: Jul 12, 2021
• Actual Study Completion Date: Aug 20, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bupivacaine + CBD (clonidine, buprenorphine, dexamethasone) Patients will receive a nerve block consisting of bupivacaine plus clonidine-buprenorphine-dexamethasone (Bupivacaine-CBD)	Drug: Bupivacaine + 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; Other Names: "Marcaine" + CBD (clonidine, buprenorphine, dexamethasone)
Active Comparator: Bupivacaine Only (control arm) Patients will receive a nerve block consisting of bupivacaine only.	Drug: Bupivacaine 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; Other Names: Marcaine

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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 Outcome Measures

1. 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.

2. Quality of Recovery 15 Item Scale (QoR-15) Total Score [6 weeks post-operation]

   Quality of Recovery 15 Item Scale, total score 0-150, 150 reflecting a perfect score and better recovery.

3. 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.

4. 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.

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Pittsburgh Healthcare System	Pittsburgh	Pennsylvania	United States	15240

Sponsors and Collaborators

• Brian Williams
• University of Pittsburgh

Investigators

• Principal Investigator: Brian Williams, MD, MBA, VA Pittsburgh Healthcare System

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 12, 2018
• Informed Consent Form - Jan 11, 2018

More Information

Publications

None provided.

• Responsible Party: Brian Williams, VAPHS Surgical Specialties Service Line Medical Director, VA Pittsburgh Healthcare System
• ClinicalTrials.gov Identifier: NCT02891798
• Other Study ID Numbers: PRO 1357; 13232002
• First Posted: Sep 8, 2016
• Last Update Posted: Jan 14, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Brian Williams, VAPHS Surgical Specialties Service Line Medical Director, VA Pittsburgh Healthcare System: analgesia,; buprenorphine; clonidine; dexamethasone; bupivacaine; nerve block
• Additional relevant MeSH terms: Dexamethasone; Dexamethasone acetate; Clonidine; Buprenorphine; Bupivacaine; BB 1101

Study Results

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 Detail

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).

Arm/Group Title	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone)	Bupivacaine Only (Control Arm)
Arm/Group Description	Patients will receive a nerve block 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	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
Period Title: Overall Study
STARTED	62	16
COMPLETED	62	16
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone)	Bupivacaine Only (Control Arm)	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	62	16	78
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.7 (7.4)	65.6 (7.6)	66 (7.5)
Sex: Female, Male (Count of Participants)
Female	6 9.7%	3 18.8%	9 11.5%
Male	56 90.3%	13 81.3%	69 88.5%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	53 85.5%	15 93.8%	68 87.2%
African American	8 12.9%	1 6.3%	9 11.5%
Other	1 1.6%	0 0%	1 1.3%
Hispanic	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	62 100%	16 100%	78 100%
BMI (kg/m^2) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	32.6 (4.6)	31.9 (5.1)	32 (5)
Diabetes (participants) [Number]
Number [participants]	23 37.1%	6 37.5%	29 37.2%

Outcome Measures

1. Primary Outcome

Title	Short-Form McGill Pain Questionnaire (Version 2) Total Score Difference From Baseline
Description	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)

Outcome Measure Data

Analysis Population Description

All participants who completed the protocol.

Arm/Group Title	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone)	Bupivacaine Only (Control Arm)
Arm/Group Description	Patients will receive a nerve block 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/Hip replacements	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/Hip replacements
Measure Participants	62	16
Mean (Standard Deviation) [score on a scale]	-1.85 (2.04)	-0.05 (2.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone), Bupivacaine Only (Control Arm)
	Comments	Comparison of SF-MPQ2 Total Score Difference From Baseline between the 4-drug nerve block group and the bupivacaine only group
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	SF-MPQ2 Continuous Pain Subscore Difference From Baseline
Description	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)

Outcome Measure Data

Analysis Population Description

All participants who completed the protocol.

Arm/Group Title	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone)	Bupivacaine Only (Control Arm)
Arm/Group Description	Patients will receive a nerve block 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/Hip replacements	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/Hip replacements
Measure Participants	62	16
Mean (Standard Deviation) [units on a scale]	-2.29 (2.43)	0.33 (2.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone), Bupivacaine Only (Control Arm)
	Comments	Comparison of SF-MPQ2 Continuous Pain Subscore Difference From Baseline between the 4-drug nerve block group and the bupivacaine only group
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	t-test, 2 sided
	Comments

3. Primary Outcome

Title	SF-MPQ2 Intermittent Pain Subscore Difference From Baseline
Description	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)

Outcome Measure Data

Analysis Population Description

All participants who completed the protocol.

Arm/Group Title	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone)	Bupivacaine Only (Control Arm)
Arm/Group Description	Patients will receive a nerve block 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/Hip replacements	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/Hip replacements
Measure Participants	62	16
Mean (Standard Deviation) [units on a scale]	-2.79 (2.66)	-1.14 (3.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone), Bupivacaine Only (Control Arm)
	Comments	Comparison of SF-MPQ2 Intermittent Pain Subscore Difference From Baseline between the 4-drug nerve block group and the bupivacaine only group
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.038
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Quality of Recovery 15 Item Scale (QoR-15) Total Score
Description	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)

Outcome Measure Data

Analysis Population Description

All participants who completed the protocol. There was missing data for one participant in the Bupivacaine Only arm.

Arm/Group Title	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone)	Bupivacaine Only (Control Arm)
Arm/Group Description	Patients will receive a nerve block 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/Hip replacements	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/Hip replacements
Measure Participants	62	15
Mean (Standard Deviation) [score on a scale]	106.08 (19.76)	90.13 (24.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone), Bupivacaine Only (Control Arm)
	Comments	Comparison of QoR-15 Total Score at post-operative day 1 between the 4-drug nerve block group and the bupivacaine only group
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Quality of Recovery 15 Item Scale (QoR-15) Total Score
Description	Quality of Recovery 15 Item Scale, total score 0-150, 150 reflecting a perfect score and better recovery.
Time Frame	6 weeks post-operation

Outcome Measure Data

Analysis Population Description

All participants who completed the protocol. There was missing data for one participant in the Bupivacaine + BCD arm.

Arm/Group Title	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone)	Bupivacaine Only (Control Arm)
Arm/Group Description	Patients will receive a nerve block 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/Hip replacements	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/Hip replacements
Measure Participants	61	16
Mean (Standard Deviation) [score on a scale]	128.89 (24.26)	130.06 (21.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone), Bupivacaine Only (Control Arm)
	Comments	Comparison of QoR-15 Total Score at 6 week post-procedure between the 4-drug nerve block group and the bupivacaine only group
	Type of Statistical Test	Non-Inferiority
	Comments	Testing the null hypothesis that Bupivacaine + BCD (buprenorphine, clonidine, dexamethasone) does not adversely affect recovery by producing a significantly lower score for the QoR-15 Total Score.
Statistical Test of Hypothesis	p-Value	0.861
	Comments
	Method	t-test, 2 sided
	Comments

6. Secondary Outcome

Title	Performed-based Physical Function is Assessed Using the Standing Balance Test.
Description	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

Outcome Measure Data

Analysis Population Description

All participants who completed the protocol. There was missing data for four participants in the Bupivacaine + BCD arm.

Arm/Group Title	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone)	Bupivacaine Only (Control Arm)
Arm/Group Description	Patients will receive a nerve block 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/Hip replacements	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/Hip replacements
Measure Participants	58	16
Mean (Standard Deviation) [score on a scale]	3.86 (0.44)	3.94 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone), Bupivacaine Only (Control Arm)
	Comments	Comparison of Standing Balance Test score at 6 week post-procedure between the 4-drug nerve block group and the bupivacaine only group
	Type of Statistical Test	Non-Inferiority
	Comments	Testing the null hypothesis that Bupivacaine + BCD (buprenorphine, clonidine, dexamethasone) does not adversely affect recovery by producing a significantly lower score for the Standing Balance test.
Statistical Test of Hypothesis	p-Value	0.512
	Comments
	Method	t-test, 2 sided
	Comments

7. Secondary Outcome

Title	Performed-based Physical Function is Assessed Using the Self-Selected Gait Speed Test.
Description	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

Outcome Measure Data

Analysis Population Description

All of the participants who completed the protocol. There was missing data for four participants in the Bupivacaine + BCD arm.

Arm/Group Title	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone)	Bupivacaine Only (Control Arm)
Arm/Group Description	Patients will receive a nerve block 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/Hip replacements	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/Hip replacements
Measure Participants	58	16
Mean (Standard Deviation) [meters per second]	0.88 (0.20)	0.94 (0.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone), Bupivacaine Only (Control Arm)
	Comments	Comparison of Self-Selected Gait Speed rate at 6 week post-procedure between the 4-drug nerve block group and the bupivacaine only group.
	Type of Statistical Test	Non-Inferiority
	Comments	Testing the null hypothesis that Bupivacaine + BCD (buprenorphine, clonidine, dexamethasone) does not adversely affect recovery by producing a significantly slower rate for the Self-Selected Gait Speed test.
Statistical Test of Hypothesis	p-Value	0.339
	Comments
	Method	t-test, 2 sided
	Comments

8. Secondary Outcome

Title	Performed-based Physical Function is Assessed Using the Repeated Chair Stand Test.
Description	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

Outcome Measure Data

Analysis Population Description

All participants who completed the protocol. There was missing data for five participants in the Bupivacaine + BCD arm.

Arm/Group Title	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone)	Bupivacaine Only (Control Arm)
Arm/Group Description	Patients will receive a nerve block 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/Hip replacements	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/Hip replacements
Measure Participants	57	16
Mean (Standard Deviation) [seconds]	12.34 (4.31)	11.93 (2.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone), Bupivacaine Only (Control Arm)
	Comments	Comparison of Repeated Chair Stand time at 6 week post-procedure between the 4-drug nerve block group and the bupivacaine only group.
	Type of Statistical Test	Non-Inferiority
	Comments	Testing the null hypothesis that Bupivacaine + BCD (buprenorphine, clonidine, dexamethasone) does not adversely affect recovery by producing a significantly slower time for the Repeated Chair Stand test.
Statistical Test of Hypothesis	p-Value	0.711
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Throughout hospitalization, and at 2-week and 6-week postoperative visits.
Adverse Event Reporting Description	Adverse events reported here only include those that were unexpected in the normal course of surgery/anesthesia.
Arm/Group Title	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone)		Bupivacaine Only (Control Arm)
Arm/Group Description	Patients will receive a nerve block consisting of bupivacaine plus buprenorphine-clonidine-dexamethasone (Bupivacaine-BCD) Bupivacaine + CBD (clonidine, buprenorphine, dexamethasone): Nerve blocks before surgery of L2-L4 and L4-S3 for Knee/Hip replacements		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/Hip replacements
All Cause Mortality
	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone)		Bupivacaine Only (Control Arm)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0%)		0/16 (0%)
Serious Adverse Events
	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone)		Bupivacaine Only (Control Arm)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone)		Bupivacaine Only (Control Arm)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/62 (1.6%)		0/16 (0%)
Musculoskeletal and connective tissue disorders
Foot drop	1/62 (1.6%)	1	0/16 (0%)	0

Limitations/Caveats

The sample size determined before the study began was N=100 patients to undergo primary THA and N=100 patients to undergo primary TKA, with these patients not undergoing physical therapy until day-one after surgery; these sample sizes were ultimately not achieved. By early 2018, same-day physical therapy (after surgery) became the new hospital guideline for patients undergoing primary THA and TKA, such that by mid-2018, the study was interrupted. Only the described 78 patients completed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.