Steroid-Enhanced Nerve Block vs Exparel for Knee Surgery Pain Management

(Yale SEVEN Trial)

Recruiting at 1 trial location

Overseen By Jinlei Li, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Opioids, Marijuana

Disqualifiers: Pregnancy, Diabetes, Immune compromise, 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: 54

Duration: Immediate post-surgery

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing two different mixes of pain relief drugs to see which works better for patients having both knees replaced. The treatments aim to reduce inflammation and numb the surgical area, with one mix using a long-lasting painkiller and the other using steroids.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on opioids or have certain conditions like uncontrolled diabetes or severe liver or kidney issues, you may not be eligible to participate.

Is liposomal bupivacaine (Exparel) safe for use in humans?

Liposomal bupivacaine (Exparel) is generally considered safe for use in humans, but there have been reports of temporary nerve issues when injected near nerves, such as in hip surgeries. It's important for doctors to be careful with its placement to avoid these problems. ^{1 2 3 4 5}

How does the drug Exparel differ from other pain management options for knee surgery?

Exparel, a long-acting local anesthetic, is unique because it uses a liposomal formulation of bupivacaine that allows for extended pain relief when injected into the surgical site, potentially reducing the need for opioids. However, studies show mixed results on its effectiveness compared to standard local anesthetics, and it may not always provide a significant advantage in pain management. ^{2 3 5 6 7}

What data supports the effectiveness of the drug used in the trial 'Steroid-Enhanced Nerve Block vs Exparel for Knee Surgery Pain Management'?

Liposomal bupivacaine (Exparel) has been shown to reduce postoperative pain and the need for opioids compared to a placebo, but its advantage over standard treatments is limited. In some studies, it did not show significant improvement over other local anesthetics, and its use in peripheral nerve blocks was often less effective than unencapsulated bupivacaine. ^{1 2 3 5 6}

Who Is on the Research Team?

Jinlei Li, MD PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults who are scheduled for elective, primary, bilateral knee replacement surgery and can receive spinal anesthesia with bupivacaine. They should not be pregnant, have coagulopathy or severe liver/renal issues, use opioids recently, or have certain conditions like uncontrolled diabetes.

Inclusion Criteria

I am scheduled for knee replacement surgery under spinal anesthesia.

Exclusion Criteria

Refusal of consent

Conditions making the patient unable to fill out questionnaire online, through email or over the phone including with cognitive dysfunction, psychiatric disorder, or non-English speaking patients, or lack of internet access which would prevent post discharge follow-up electronically

I have not used opioids or regularly used marijuana in the month before my surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nerve block treatments with B-LB and B-DEX-MPA during bilateral total knee arthroplasty

Immediate post-surgery

In-hospital stay up to 48 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pain and functional assessments

3 months

Multiple assessments at baseline, 6 weeks, and 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Bupivacaine-Liposomal Bupivacaine
• Dexamethasone Sodium Phosphate-Methylprednisolone Acetate

Trial Overview The study compares two pain control methods after knee surgery: one combines dexamethasone and methylprednisolone with bupivacaine (B-DEX-MPA), while the other uses liposomal bupivacaine with plain bupivacaine (B-LB). It aims to see which provides better pain relief and recovery quality.

How Is the Trial Designed?

Group I: B-LB in right knee and B-DEX-MPA in left knee Experimental Treatment 2 Interventions

Participants in this arm will receive B-LB in their right knee and B-DEX-MPA in their left knee. Nerve block with (B-LB): A medication mixture of 40 ml (20 ml LB and 20 ml 0.25% plain bupivacaine) will be prepared, of which 20 ml will be used in Adductor canal block, 10 ml will be used in iPACK block and 5 ml each will be used in medial upper and lateral upper genicular nerve block, respectively. Nerve block with (B-DEX-MPA): A medication mixture of 40 ml (40 ml 0.25% plain bupivacaine, 10 mg DEX and 80 mg MPA) will be prepared, of which 20 ml will be used in Adductor canal block, 10 ml will be used in iPACK block and 5 ml each will be used in medial upper and lateral upper genicular nerve block, respectively.

Group II: B-LB in left knee and B-DEX-MPA in right knee Experimental Treatment 2 Interventions

Participants in this arm will receive B-LB in their left knee and B-DEX-MPA in their right knee. Nerve block with (B-LB): A medication mixture of 40 ml (20 ml LB and 20 ml 0.25% plain bupivacaine) will be prepared, of which 20 ml will be used in Adductor canal block, 10 ml will be used in iPACK block and 5 ml each will be used in medial upper and lateral upper genicular nerve block, respectively. Nerve block with (B-DEX-MPA): A medication mixture of 40 ml (40 ml 0.25% plain bupivacaine, 10 mg DEX and 80 mg MPA) will be prepared, of which 20 ml will be used in Adductor canal block, 10 ml will be used in iPACK block and 5 ml each will be used in medial upper and lateral upper genicular nerve block, respectively.

Bupivacaine-Liposomal Bupivacaine is already approved in United States, European Union for the following indications:

Approved in United States as Exparel for:

• Postsurgical local analgesia
• Interscalene brachial plexus nerve block
• Adductor canal block
• Sciatic nerve block in the popliteal fossa

Approved in European Union as Exparel for:

• Postsurgical local analgesia

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Department of Anesthesiology Faculty Development Fund

Collaborator

Trials

2

Recruited

320+

Published Research Related to This Trial

In a retrospective analysis of 575 subjects across 6 clinical trials, liposome bupivacaine showed a similar safety profile to both bupivacaine HCl and normal saline, with 76% of liposome bupivacaine recipients experiencing adverse events (AEs).

The most common AEs for liposome bupivacaine included nausea and hypesthesia, and serious AEs occurred in 8% of subjects, indicating that the side effects are likely related to the surgical procedure rather than the medication itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Side Effect Profile of Liposome Bupivacaine (Exparel) in Peripheral Nerve Blocks. Ilfeld, BM., Viscusi, ER., Hadzic, 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]

A review of 76 randomized controlled trials found that only 11% showed a significant benefit of liposomal bupivacaine over standard bupivacaine or ropivacaine for postoperative pain control.

The majority of trials indicated that unencapsulated bupivacaine provided better pain relief than liposomal bupivacaine, suggesting that routine use of liposomal bupivacaine may not be justified based on current evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Effectiveness of Liposomal Bupivacaine Administered by Infiltration or Peripheral Nerve Block to Treat Postoperative Pain. Ilfeld, BM., Eisenach, JC., Gabriel, RA.[2021]

In a study of 100 patients undergoing total knee arthroplasties, liposomal bupivacaine (Exparel) used in adductor canal blocks significantly reduced hospital stay length (36.3 hours vs. 49.7 hours) and decreased inpatient opioid use (40.9 MME/d vs. 47.3 MME/d).

Patients receiving Exparel reported better pain relief at all postoperative time points and showed greater improvements in their WOMAC scores, indicating enhanced recovery and pain management compared to those receiving ropivacaine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal Bupivacaine in Adductor Canal Blocks Before Total Knee Arthroplasty Leads to Improved Postoperative Outcomes: A Randomized Controlled Trial. Malige, A., Pellegrino, AN., Kunkle, K., et al.[2022]

In a study involving 59 patients undergoing total knee arthroplasty, liposomal bupivacaine did not show a significant clinical advantage over standard bupivacaine in terms of postoperative recovery, as measured by the number of physical therapy sessions needed for discharge.

The use of liposomal bupivacaine was associated with higher medication charges, raising concerns about its cost-effectiveness compared to standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal Bupivacaine Versus Standard Periarticular Injection in Total Knee Arthroplasty With Regional Anesthesia: A Prospective Randomized Controlled Trial. Hyland, SJ., Deliberato, DG., Fada, RA., et al.[2019]

In three cases of total hip arthroplasty using liposomal bupivacaine (Exparel®), patients experienced temporary loss of function in the sciatic nerve area for 24 to 72 hours post-surgery, likely due to the medication being injected too close to the nerve.

These neurological deficits have not been previously reported in the literature, highlighting the need for careful administration of liposomal bupivacaine to prevent such complications during orthopedic procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unanticipated transient sciatic nerve deficits from intra-wound liposomal bupivacaine injection during total hip arthroplasty. Bronson, WH., Doran, JP., Slover, J., et al.[2020]

EXPAREL® (bupivacaine liposome injectable suspension) has been shown to effectively reduce postoperative pain and opioid use in patients undergoing hip and knee arthroplasty, offering a safer alternative to traditional peripheral nerve blocks.

In a pilot study, patients receiving EXPAREL® reported lower pain scores and experienced significant cost savings of $411 for total knee arthroplasty and $348 for total hip arthroplasty compared to those receiving nerve blocks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transition from nerve blocks to periarticular injections and emerging techniques in total joint arthroplasty. Springer, BD.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Safety and Side Effect Profile of Liposome Bupivacaine (Exparel) in Peripheral Nerve Blocks. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Perineural dexamethasone attenuates liposomal bupivacaine-induced delayed neural inflammation in mice in vivo. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Clinical Effectiveness of Liposomal Bupivacaine Administered by Infiltration or Peripheral Nerve Block to Treat Postoperative Pain. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Liposomal Bupivacaine in Adductor Canal Blocks Before Total Knee Arthroplasty Leads to Improved Postoperative Outcomes: A Randomized Controlled Trial. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Liposomal Bupivacaine Versus Standard Periarticular Injection in Total Knee Arthroplasty With Regional Anesthesia: A Prospective Randomized Controlled Trial. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Unanticipated transient sciatic nerve deficits from intra-wound liposomal bupivacaine injection during total hip arthroplasty. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Transition from nerve blocks to periarticular injections and emerging techniques in total joint arthroplasty. [2022]