PainPhase 3NCT02891798

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

A Phase 3 study testing Bupivacaine + CBD (clonidine, buprenorphine, dexamethasone) in people with Pain, run by Brian Williams at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 85 years
Conditions the study is for: Pain
What is being tested?: Bupivacaine + CBD (clonidine, buprenorphine, dexamethasone)
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 98 participants
Where: 1 siteUnited States
Study dates: Oct 2016to 20 Aug 2021
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age between 18 and 85, and undergoing a total knee or hip replacement.
Fluent in English, decision competent, willing and able to provide written informed consent, and able to complete the study's schedule of assessments.
Able to walk >3m without an assisting device.
Have a BMI ≤ 40 kg/m2.

Who cannot join

Current participation in another orthopedic/Physical Therapy/rehab/anesthesiology interventional clinical trial.
Are at significant behavioral risks or have refractory major psychiatric disorders.
Revision surgery on the same extremity.
Have an American Surgical Association (ASA) Physical Status classification of 4 or higher.
Have been diagnosed with clinically significant neuropathy with its origins in either diabetes or other causes; have neuromuscular disease that would influence data collection.
Have a surgically-fused lumbar spine, or a spinal cord simulator, or other condition that would contraindicate or prohibit the conduct of spinal anesthesia.

Show all 17Show fewer

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.
Are undergoing Total Knee Arthroplasty (TKA)/Total Hip Arthroplasty (THA) for a tumor.
Have contraindications (e.g., anaphylaxis) to any of the study drugs.
Have a systemic fungal infection.
Have a known hypersensitivity to bupivacaine hydrochloride or to any local anesthetic of the amide-type or to other components of bupivacaine hydrochloride solutions.
Have a known or suspected buprenorphine hypersensitivity (not including nausea and/or vomiting).
Have a gastro-intestinal (GI) obstruction.
Have paralytic ileus.
Pregnant women
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.

Trial locations and contacts

1 site in 1 country.

United States1 site

VA Pittsburgh Healthcare System
Pittsburgh, Pennsylvania, 15240

Other trials in United States

About this study

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).

Read the detailed description

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

Conditions: Pain
Being tested: Bupivacaine + CBD (clonidine, buprenorphine, dexamethasone), Bupivacaine Only (control arm)
Keywords: analgesia,, buprenorphine, clonidine, dexamethasone, bupivacaine, nerve block
Medical subject headings: Pain, Agnosia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Bupivacaine + CBD (clonidine, buprenorphine, dexamethasone)Drug
Also called "Marcaine" + 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
Bupivacaine Only (control arm)Drug
Also called Marcaine
Nerve blocks before surgery of L2-L4 and L4-S3 for Knee replacements Nerve blocks before surgery of L2-L4 for hip replacements

Study groups in NCT02891798
Study group	Role	What they receive
Bupivacaine + CBD (clonidine, buprenorphine, dexamethasone)	Experimental	Patients will receive a nerve block consisting of bupivacaine plus clonidine-buprenorphine-dexamethasone (Bupivacaine-CBD) Receives: Drug: Bupivacaine + CBD (clonidine, buprenorphine, dexamethasone)
Bupivacaine Only (control arm)	Active comparator	Patients will receive a nerve block consisting of bupivacaine only. Receives: Drug: Bupivacaine Only (control arm)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline, Post-Operative day after surgery (7AM-9AM EST)
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.
Measured: Baseline, Post-Operative day after surgery (7AM-9AM EST)
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.
Measured: Baseline, Post-Operative day after surgery (7AM-9AM EST)

Secondary outcomes (5)

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.
Measured: Day after surgery (7AM-9AM EST)
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.
Measured: 6 weeks post-operation
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.
Measured: 6 weeks post-operation
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.
Measured: 6 weeks post-operation
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.
Measured: 6 weeks post-operation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 201620 Aug 2021

First posted8 Sep 2016 (estimated)
Study startOct 2016
Primary completion12 Jul 2021
Study completion20 Aug 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for PainStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 98 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02891798
Sponsor's protocol ID: PRO 1357
Other IDs: 13232002
Status last verified: Jan 2022
First submitted: 12 Aug 2016
Last updated: 14 Jan 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

Aloziem OU, Williams BA, Mikolic JM, Boudreaux-Kelly MY, Faruque S, Piva SR, Ibinson JW, Switzer GE. Assessing Common Content and Responsiveness of the QoR-15 and the SF-8 in the Context of Recovery from Regional Anesthesia for Joint Replacement. Mil Med. 2023 Nov 3;188(11-12):e3469-e3476. doi: 10.1093/milmed/usad191.
PubMed 37256753
Williams BA, Ibinson JW, Mikolic JM, Boudreaux-Kelly MY, Paiste HJ, Gilbert KL, Bonant SA, Ritter ME, Ezaru CS, Muluk VS, Piva SR. Day-One Pain Reductions After Hip and Knee Replacement When Buprenorphine-Clonidine-Dexamethasone Is Added to Bupivacaine Nerve/Plexus Blocks: A Randomized Clinical Trial. Pain Med. 2022 Jan 3;23(1):57-66. doi: 10.1093/pm/pnab325.
PubMed 34730810

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 14 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 4-drug Nerve Block Versus Plain Local Anesthetic for Knee and Hip Arthroplasty Analgesia in Veterans
ClinicalTrials.gov ID: NCT02891798
Acronym / sponsor ID: PRO 1357
Conditions: Pain
Keywords: analgesia,, buprenorphine, clonidine, dexamethasone, bupivacaine, nerve block
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 98 participants (actual)
Lead sponsor: Brian WilliamsUS federal agency
Collaborators: University of Pittsburgh
Study start: Oct 2016
Primary completion: 12 Jul 2021 (actual)
Study completion: 20 Aug 2021 (actual)
First posted: 8 Sep 2016 (estimated)
Results: Posted 20 Dec 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Bupivacaine + CBD (clonidine, buprenorphine, dexamethasone)	Experimental	Drug: Bupivacaine + CBD (clonidine, buprenorphine, dexamethasone)Patients will receive a nerve block consisting of bupivacaine plus clonidine-buprenorphine-dexamethasone (Bupivacaine-CBD)
Bupivacaine Only (control arm)	Active comparator	Drug: Bupivacaine Only (control arm)Patients will receive a nerve block consisting of bupivacaine only.

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Age between 18 and 85, and undergoing a total knee or hip replacement.
Fluent in English, decision competent, willing and able to provide written informed consent, and able to complete the study's schedule of assessments.
Able to walk >3m without an assisting device.
Have a BMI ≤ 40 kg/m2.

Key exclusion criteria (17 listed)

Current participation in another orthopedic/Physical Therapy/rehab/anesthesiology interventional clinical trial.
Are at significant behavioral risks or have refractory major psychiatric disorders.
Revision surgery on the same extremity.
Have an American Surgical Association (ASA) Physical Status classification of 4 or higher.
Have been diagnosed with clinically significant neuropathy with its origins in either diabetes or other causes; have neuromuscular disease that would influence data collection.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Bupivacaine + CBD (clonidine, buprenorphine, dexamethasone)Also: "Marcaine" + 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	Drug	Bupivacaine + CBD (clonidine, buprenorphine, dexamethasone)
Bupivacaine Only (control arm)Also: MarcaineNerve blocks before surgery of L2-L4 and L4-S3 for Knee replacements Nerve blocks before surgery of L2-L4 for hip replacements	Drug	Bupivacaine Only (control arm)

Primary outcome

Short-Form McGill Pain Questionnaire (Version 2) Total Score Difference From Baseline
Time frame: 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
Time frame: 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
Time frame: 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.

5 secondary outcomes

Quality of Recovery 15 Item Scale (QoR-15) Total Score
Time frame: Day after surgery (7AM-9AM EST)
Quality of Recovery 15 Item Scale (QoR-15) Total Score
Time frame: 6 weeks post-operation
Performed-based Physical Function is Assessed Using the Standing Balance Test.
Time frame: 6 weeks post-operation
Performed-based Physical Function is Assessed Using the Self-Selected Gait Speed Test.
Time frame: 6 weeks post-operation
Performed-based Physical Function is Assessed Using the Repeated Chair Stand Test.
Time frame: 6 weeks post-operation

Results and safety

Results posted to the registry on 20 Dec 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone)	62	62
Bupivacaine Only (Control Arm)	16	16

Primary outcome: Short-Form McGill Pain Questionnaire (Version 2) Total Score Difference From Baseline

Time frame: Baseline, Post-Operative day after surgery (7AM-9AM EST). Mean (Standard Deviation). Unit: score on a scale

Measure	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone) n = 62	Bupivacaine Only (Control Arm) n = 16
Value	-1.85 (2.04)	-0.05 (2.38)

Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone) vs Bupivacaine Only (Control Arm): p = 0.003, t-test, 2 sided

Population analysed: All participants who completed the protocol.

Primary outcome: SF-MPQ2 Continuous Pain Subscore Difference From Baseline

Time frame: Baseline, Post-Operative day after surgery (7AM-9AM EST). Mean (Standard Deviation). Unit: units on a scale

Measure	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone) n = 62	Bupivacaine Only (Control Arm) n = 16
Value	-2.29 (2.43)	0.33 (2.76)

Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone) vs Bupivacaine Only (Control Arm): p = 0.001, t-test, 2 sided

Population analysed: All participants who completed the protocol.

Primary outcome: SF-MPQ2 Intermittent Pain Subscore Difference From Baseline

Time frame: Baseline, Post-Operative day after surgery (7AM-9AM EST). Mean (Standard Deviation). Unit: units on a scale

Measure	Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone) n = 62	Bupivacaine Only (Control Arm) n = 16
Value	-2.79 (2.66)	-1.14 (3.27)

Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone) vs Bupivacaine Only (Control Arm): p = 0.038, t-test, 2 sided

Population analysed: All participants who completed the protocol.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Throughout hospitalization, and at 2-week and 6-week postoperative visits.. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Bupivacaine + BCD (Buprenorphine, Clonidine, Dexamethasone)	0 of 62 (0%)	1 of 62 (1.6%)	0 of 62
Bupivacaine Only (Control Arm)	0 of 16 (0%)	0 of 16 (0%)	0 of 16

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37256753Aloziem OU, Williams BA, Mikolic JM, Boudreaux-Kelly MY, Faruque S, Piva SR, Ibinson JW, Switzer GE. Assessing Common Content and Responsiveness of the QoR-15 and the SF-8 in the Context of Recovery from Regional Anesthesia for Joint Replacement. Mil Med. 2023 Nov 3;188(11-12):e3469-e3476. doi: 10.1093/milmed/usad191.
Derived from this study: PubMed 34730810Williams BA, Ibinson JW, Mikolic JM, Boudreaux-Kelly MY, Paiste HJ, Gilbert KL, Bonant SA, Ritter ME, Ezaru CS, Muluk VS, Piva SR. Day-One Pain Reductions After Hip and Knee Replacement When Buprenorphine-Clonidine-Dexamethasone Is Added to Bupivacaine Nerve/Plexus Blocks: A Randomized Clinical Trial. Pain Med. 2022 Jan 3;23(1):57-66. doi: 10.1093/pm/pnab325.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Brian Williams, MD, MBA principal investigator

VA Pittsburgh Healthcare System

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bupivacaine + CBD (clonidine, buprenorphine, dexamethasone) in people with Pain, run by Brian Williams at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Short-Form McGill Pain Questionnaire (Version 2) Total Score Difference From Baseline (time frame: Baseline, Post-Operative day after surgery (7AM-9AM EST)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02891798, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2022.