Exparel for Postoperative Pain

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Campbell Clinic

Must not be taking: Opioids, NSAIDs

Disqualifiers: Addiction, Psychiatric disorders, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

Duration: Day of surgery

10 Participants Needed

Trial Summary

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 have a condition that requires pain medication not related to the knee surgery, it might affect your eligibility. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Exparel for postoperative pain?

Exparel, a long-acting form of bupivacaine, has been shown to provide effective pain relief in orthopedic trauma surgeries, helping patients manage pain after surgery. It is part of a multimodal pain management approach, which means it is used alongside other pain relief methods to improve overall pain control. ^{1 2 3 4 5}

Is Exparel safe for use in humans?

Exparel, a long-acting form of bupivacaine, has been shown to be safe for use in various surgical procedures, including breast augmentation and orthopedic trauma surgery, providing effective pain relief with minimal side effects. ^{1 2 3 5 6}

What makes the drug Exparel unique for postoperative pain management?

Exparel is unique because it is an extended-release formulation of bupivacaine, allowing for a single-dose injection directly into the surgical site to provide long-lasting pain relief after surgery. This reduces the need for additional pain medications, including opioids, and is part of a multimodal approach to pain management. ^{1 2 3 5 7}

What is the purpose of this trial?

This is a case series to assess the clinical utility of an Intra-articular Posteromedial Surgeon Administered (IPSA) Block in patients undergoing primary unilateral total knee arthroplasty.

Research Team

William Mihalko, MD, PhD

Principal Investigator

Campbell Clinic

Eligibility Criteria

This trial is for patients undergoing primary unilateral total knee arthroplasty to manage postoperative pain and osteoarthritis. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and not have conditions that would exclude them from safely receiving the intervention.

Inclusion Criteria

Able to provide informed consent, adhere to study schedule, and complete all study assessments

Body Mass Index (BMI) > 18 and < 40 kg/m2

I am in good to moderate health with or without severe systemic disease.

Exclusion Criteria

Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the Investigator, could interfere with study assessments or compliance

Clinically significant medical disease that, in the opinion of the Investigator, would make participation in a clinical study inappropriate. This includes diabetic neuropathy, coagulation or bleeding disorders, severe peripheral vascular disease, renal insufficiency, hepatic dysfunction or other conditions that would constitute a contraindication to participation in the study

History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Patients receive an EXPAREL IPSA block intraoperatively during primary unilateral total knee arthroplasty

Day of surgery

1 visit (in-person)

Immediate Post-operative Monitoring

Monitoring of vital signs and pain levels in PACU and up to 72 hours post-surgery

3 days

Continuous monitoring in PACU

Follow-up

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

6 weeks

Post-operative Day 14 and Day 42 visits (in-person)

Treatment Details

Interventions

• Exparel

Trial Overview The clinical utility of an Intra-articular Posteromedial Surgeon Administered (IPSA) Block using Exparel is being assessed. This involves a surgeon directly administering the medication into the joint during knee replacement surgery to control pain after the operation.

Participant Groups

Group I: Experimental Group Experimental Treatment 1 Intervention

Patients will receive an EXPAREL IPSA block intraoperatively.

Exparel is already approved in United States for the following indications:

Approved in United States as Exparel for:

• Postsurgical local analgesia via infiltration in patients aged 6 years and older
• Postsurgical regional analgesia via an interscalene brachial plexus block in adults
• Postsurgical regional analgesia via a sciatic nerve block in the popliteal fossa in adults
• Postsurgical regional analgesia via an adductor canal block in adults

Who Is Running the Clinical Trial?

Campbell Clinic

Lead Sponsor

Trials

15

Recruited

2,100+

Findings from Research

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]

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]

Liposomal bupivacaine (Exparel) has been shown to be a safe and effective option for managing postoperative pain in plastic surgery, based on a review of eight studies involving 405 patients.

Compared to traditional pain management methods, liposomal bupivacaine was found to be equivalent or more effective, suggesting it could serve as a less invasive alternative to more complex pain management systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of Liposomal Bupivacaine (Exparel) for Postoperative Analgesia. Vyas, KS., Rajendran, S., Morrison, SD., et al.[2022]

EXPAREL® (bupivacaine liposome injectable suspension) is an effective extended-release local anesthetic that can significantly improve postoperative pain management in orthopedic trauma surgery, as demonstrated in two case studies.

Both patients treated with EXPAREL® experienced good control of postsurgical pain, highlighting its safety and efficacy as part of a multimodal analgesia approach in reducing the risk of chronic pain after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local infiltration of liposome bupivacaine in orthopedic trauma patients: case-based reviews. Hutchinson, HL.[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]

EXPAREL® (bupivacaine liposome injectable suspension) is an FDA-approved extended-release anesthetic that significantly reduces postoperative pain and opioid consumption in patients undergoing total knee and hip replacement surgeries, as shown in multiple phase 2 and phase 3 studies.

Using EXPAREL® as part of a multimodal pain management approach leads to better outcomes, including lower pain scores, reduced need for rescue opioids, and improved patient satisfaction during recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in incorporation of local analgesics in postsurgical pain pathways. Lombardi, AV.[2014]

References

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. England pubmed.ncbi.nlm.nih.gov

Neurological and histological outcomes after subarachnoid injection of a liposomal bupivacaine suspension in pigs: a pilot study. [2019]

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

Systematic Review of Liposomal Bupivacaine (Exparel) for Postoperative Analgesia. [2022]

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

Local infiltration of liposome bupivacaine in orthopedic trauma patients: case-based reviews. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Bupivacaine Versus Liposomal Bupivacaine for Postoperative Pain Control after Augmentation Mammaplasty: A Prospective, Randomized, Double-Blind Trial. [2022]

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

Recent advances in incorporation of local analgesics in postsurgical pain pathways. [2014]