Pain Control for Total Shoulder Replacement

Overseen By Heinz Hoenecke, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Scripps Clinic

Must not be taking: Narcotics, Oxycodone, Celebrex

Disqualifiers: Drug abuse, Neurological deficit, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two approaches to managing pain after shoulder replacement surgery. Researchers compare a standard pain-relief injection with a new formula that includes liposomal bupivacaine, a long-acting local anesthetic that might offer longer-lasting relief. They examine how well each method controls pain, reduces the need for narcotics, and improves patient satisfaction and function. This trial suits individuals undergoing their first shoulder replacement surgery who are not currently using narcotics. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, allowing researchers to understand its benefits for more patients.

Do I need to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have used narcotics in the last 3 months or if you have certain allergies or intolerances.

What is the safety track record for bupivacaine and liposomal bupivacaine?

A previous study showed that liposomal bupivacaine effectively managed pain after shoulder replacement surgery. Patients reported more manageable pain levels, suggesting its effectiveness in pain reduction.

The regular version, bupivacaine, is also commonly used for pain relief during surgeries. Research has shown that it is generally well-tolerated by patients when used in interscalene nerve blocks, a type of anesthesia for shoulder surgery.

Since this trial is in Phase 4, both treatments have already been approved and used safely for other conditions. Phase 4 trials typically confirm ongoing safety and effectiveness in a wider range of people. Thus, substantial information suggests both forms of bupivacaine are safe for human use. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the combination of bupivacaine and liposomal bupivacaine for pain control in total shoulder replacement because it offers a potentially longer-lasting effect than the standard bupivacaine treatment. While typical pain management uses bupivacaine alone, the addition of liposomal bupivacaine allows for a slow release of the drug, which can extend pain relief significantly. This extended action can mean less frequent dosing and potentially better pain management, which is a significant improvement over current options.

What evidence suggests that this trial's treatments could be effective for pain control in total shoulder replacement?

This trial will compare the effectiveness of liposomal bupivacaine with traditional bupivacaine for pain control after total shoulder replacement. Studies have shown that liposomal bupivacaine reduces pain after shoulder surgery by slowly releasing the medication over time, providing longer-lasting relief. Research indicates that patients receiving liposomal bupivacaine often experience less pain and may require fewer strong painkillers after surgery, aiding recovery and increasing satisfaction. Traditional bupivacaine, not in liposome form, also alleviates pain, but the liposomal version offers longer-lasting relief. Participants in this trial will receive either an interscalene block with liposomal bupivacaine and bupivacaine or bupivacaine alone. ^{6 7 8 9 10}

Who Is on the Research Team?

Heinz Hoenecke, MD

Principal Investigator

Scripps Health

Are You a Good Fit for This Trial?

This trial is for patients between the ages of 50 and 85 who are having their first shoulder replacement surgery. It's not suitable for those with oxycodone intolerance, conditions that make interscalene block risky, active narcotic use in the past 3 months, allergy to amide anesthetics, inability to take Celebrex, or cognitive issues affecting participation.

Inclusion Criteria

I am having a shoulder replacement or reverse shoulder surgery.

Exclusion Criteria

I am under 50 years old.

I am having a second surgery on my shoulder.

I have a neurological condition affecting my movement or senses.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Assessment

Participants undergo preoperative assessment including ASES score and pain score evaluation

Up to 4 weeks

1 visit (in-person)

Treatment

Participants receive interscalene block with or without liposomal bupivacaine during shoulder arthroplasty

1 day

1 visit (in-person)

Postoperative Monitoring

Participants' narcotic and non-narcotic pain medication usage, pain severity, and satisfaction are monitored

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including ASES score and pain score evaluation

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Bupivacaine
• Liposomal bupivacaine

Trial Overview The study is testing if adding liposomal bupivacaine to a standard pain blocker (interscalene block) improves pain control after shoulder replacement surgery. Patients will be randomly assigned to receive either the new combination or just the standard treatment without knowing which one they get.

How Is the Trial Designed?

Group I: Study group Experimental Treatment 2 Interventions

The study group will receive an interscalene block consisting of 10 mL 0.5% bupivacaine and 10 mL of liposomal bupivacaine \[133mg\].

Group II: Control group Active Control 1 Intervention

The control group will receive an interscalene block consisting of 20 mL of 0.5%bupivacaine alone.

Who Is Running the Clinical Trial?

Scripps Clinic

Lead Sponsor

Trials

15

Recruited

28,400+

Published Research Related to This Trial

In a study of 491 total shoulder arthroplasty patients, those who received liposomal bupivacaine for interscalene blocks reported significantly better pain control in the first 24 hours post-surgery, with 69% achieving clinically tolerable pain compared to only 39% in the other block group and 11% in the no block group.

Patients receiving liposomal bupivacaine also had lower average pain scores and reduced opioid consumption in the first 24 hours, indicating that it may provide effective postoperative analgesia while potentially minimizing the need for opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal Bupivacaine Interscalene Blocks Demonstrate a Greater Proportion of Total Shoulder Arthroplasty Patients with Clinically Tolerable Pain - a Retrospective Quality Improvement Study of 491 Patients. Lee, JK., Greenberg, S., Wixson, R., et al.[2023]

In a pilot study involving 25 pigs, subarachnoid administration of liposomal bupivacaine resulted in a longer duration of pain relief compared to standard bupivacaine hydrochloride, with effects lasting up to 32 hours for higher doses.

No signs of neurotoxicity were observed in any treatment group, suggesting that liposomal bupivacaine may be a safe option for extended analgesia in the neuraxial space, warranting further studies for potential human use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurological and histological outcomes after subarachnoid injection of a liposomal bupivacaine suspension in pigs: a pilot study. Zel, J., Hadzic, A., Cvetko, E., et al.[2019]

In a study of 90 patients undergoing immediate breast reconstruction, the use of liposomal bupivacaine (LB) significantly reduced postoperative pain scores compared to traditional pain management methods, indicating its efficacy as a pain reliever.

Patients receiving LB also had a shorter hospital stay (1.5 days) compared to those on narcotics (2.0 days), with no reported adverse events, highlighting its safety and potential benefits in postoperative recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative Pain and Length of Stay Lowered by Use of Exparel in Immediate, Implant-Based Breast Reconstruction. Butz, DR., Shenaq, DS., Rundell, VL., et al.[2022]

In a study of 34 patients undergoing breast augmentation, liposomal bupivacaine provided statistically significant lower pain scores compared to standard bupivacaine at multiple time points post-surgery, indicating it may offer better pain control.

Despite the statistical significance, the differences in pain relief were small, and 70% of patients felt the additional cost of liposomal bupivacaine was not justified by the benefits, suggesting limited clinical relevance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupivacaine Versus Liposomal Bupivacaine for Postoperative Pain Control after Augmentation Mammaplasty: A Prospective, Randomized, Double-Blind Trial. Nadeau, MH., Saraswat, A., Vasko, A., et al.[2022]

In a study involving 98 mice, liposomal bupivacaine (Exparel®) provided a longer duration of pain relief compared to standard bupivacaine, with motor block lasting up to 180 minutes and thermoalgesic block lasting up to 420 minutes.

The addition of dexamethasone, either perineurally or systemically, significantly reduced neural inflammation caused by bupivacaine, and perineural dexamethasone also helped reduce inflammation from Exparel®, suggesting a protective effect against nerve damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perineural dexamethasone attenuates liposomal bupivacaine-induced delayed neural inflammation in mice in vivo. Ferré, F., Krin, A., Sanchez, M., et al.[2020]

In a study of 87 patients undergoing shoulder arthroplasty, local infiltration of a periarticular cocktail provided significantly better pain control immediately after surgery compared to interscalene nerve block and liposomal bupivacaine, with lower visual analog scale scores on postoperative day 0.

Patients receiving the periarticular cocktail also required significantly less opioid medication on the first day after surgery, indicating a potential for reduced opioid consumption and improved pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does the use of periarticular anesthetic cocktail provide adequate pain control following shoulder arthroplasty? Klag, EA., Okoroha, KR., Kuhlmann, NA., et al.[2022]

In a study of 565 patients undergoing total shoulder arthroplasty, liposomal bupivacaine (LB) provided significantly lower mean pain scores at 24 and 36 hours post-surgery compared to continuous interscalene catheters (CIC), indicating better postoperative pain control.

Patients receiving LB had a higher rate of opioid-free pain management (32% vs. 10%) and required less opioid escalation, suggesting that LB may reduce opioid use and associated complications in multimodal pain management for shoulder surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interscalene block with liposomal bupivacaine versus continuous interscalene catheter in primary total shoulder arthroplasty. Levin, JM., Charalambous, LT., Girden, A., et al.[2023]

In a study of 83 shoulder arthroplasty patients, the use of an indwelling interscalene nerve block (IINB) resulted in significantly lower pain scores and reduced opioid consumption immediately after surgery compared to liposomal bupivacaine (LB).

Patients receiving LB experienced higher pain levels and required more narcotics in the immediate postoperative period, indicating that IINB is a more effective pain management strategy right after shoulder surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal bupivacaine versus indwelling interscalene nerve block for postoperative pain control in shoulder arthroplasty: a prospective randomized controlled trial. Abildgaard, JT., Lonergan, KT., Tolan, SJ., et al.[2022]

A meta-analysis of four randomized controlled trials involving 510 patients showed that liposomal bupivacaine is as effective as interscalene nerve block for managing pain after total shoulder arthroplasty, with no significant differences in pain scores or opioid consumption at 12, 24, and 48 hours post-surgery.

Both treatments provided comparable pain relief and opioid-sparing effects, suggesting that liposomal bupivacaine could be a viable alternative to traditional nerve blocks, although further high-quality studies are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal bupivacaine versus interscalene nerve block for pain control after total shoulder arthroplasty: A systematic review and meta-analysis. Wang, K., Zhang, HX.[2022]

In a study of 52 patients undergoing major shoulder surgery, the addition of liposome bupivacaine to standard bupivacaine significantly reduced worst pain levels in the first postoperative week compared to standard bupivacaine alone, with a modest effect size.

Patients receiving liposome bupivacaine also reported greater overall satisfaction with their pain management, indicating that this combination may enhance postoperative recovery experiences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of Liposome Bupivacaine to Bupivacaine HCl Versus Bupivacaine HCl Alone for Interscalene Brachial Plexus Block in Patients Having Major Shoulder Surgery. Vandepitte, C., Kuroda, M., Witvrouw, R., et al.[2022]

In a study of 70 patients undergoing shoulder arthroplasty, liposomal bupivacaine (LB) provided effective postoperative pain relief comparable to continuous interscalene nerve block (CISB) within the first 24 hours, with similar narcotic use and pain scores.

LB was associated with better functional outcomes, as indicated by higher American Shoulder and Elbow Surgeons and Penn Shoulder Scores at follow-up, along with fewer complications and lower costs compared to the CISB group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective randomized controlled trial to identify the optimal postoperative pain management in shoulder arthroplasty: liposomal bupivacaine versus continuous interscalene catheter. Sabesan, VJ., Shahriar, R., Petersen-Fitts, GR., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39757893/

The Use of Liposomal Bupivacaine for Pain Control After ... Conclusion: LB is a promising anesthetic component with efficacy in providing analgesia after shoulder surgery. Single-injection LB nerve blocks ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06139666

The Effect of Liposomal Bupivacaine Nerve Block (Exparel) ... The goal of this clinical trial is to investigate if there is a difference in pain after an arthroscopic rotator cuff surgery when a nerve block is performed ...

3. journaloei.scholasticahq.com journaloei.scholasticahq.com/article/117497-liposomal-bupivacaine-in-managing-postoperative-pain-following-shoulder-surgery

Liposomal Bupivacaine in Managing Postoperative Pain ... 3% free bupivacaine provides patients with substantial, prolonged postoperative analgesia following shoulder surgery.

4. aetna.com aetna.com/cpb/medical/data/900_999/0941.html

Bupivacaine Liposome (Exparel) - Medical Clinical Policy ... The authors concluded that liposomal bupivacaine infiltration provides equivalent postoperative pain control compared with interscalene nerve block following ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28375887/

Randomized Controlled Trial of Interscalene Block ... Bupivacaine liposome injectable suspension, a sustained release preparation, is used for surgical-site administration. The purpose of this study ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5626269/

Comparison of liposomal bupivacaine infiltration versus ... This meta-analysis aimed to compare the efficiency and safety of liposomal bupivacaine infiltration and interscalene nerve block for pain control after ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03638960

Interscalene Single Shot With Plain Bupivacaine Versus ... The investigators will be comparing pain scores and opioid use in patients receiving interscalene peripheral blocks with plain bupivacaine versus those ...

8. mayo.edu mayo.edu/research/clinical-trials/tests-procedures/shoulder-replacement-surgery

Shoulder Replacement Surgery Clinical Trials The primary objective of this study is to collect and evaluate long-term clinical and radiographic outcomes data to better understand the safety and performance ...

9. jisakos.com jisakos.com/article/S2059-7754(23)00582-5/fulltext

Liposomal bupivacaine interscalene blocks demonstrate a ... Liposomal bupivacaine interscalene blocks demonstrate a greater proportion of total shoulder arthroplasty patients with clinically tolerable pain.

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28682872/

Liposomal bupivacaine versus interscalene nerve block for ... Data on patients prepared for TSA in studies that compared liposomal bupivacaine versus interscalene nerve block were retrieved. The endpoints were the visual ...