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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of Exparel, a pain relief medication, during knee replacement surgery. The goal is to determine if an injection of Exparel during surgery can better manage postoperative pain for individuals with knee osteoarthritis. Candidates for participation include those undergoing their first total knee replacement and diagnosed with knee osteoarthritis. Participants should not have other painful conditions requiring pain medication unrelated to the knee surgery. As a Phase 4 trial, Exparel has already received FDA approval and proven effective, and this research aims to understand its benefits for more patients.

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 is the safety track record for Exparel?

Research has shown that Exparel, a treatment for managing pain after surgery, is generally well-tolerated. Studies have identified fever, dizziness, and swelling as the most common side effects, occurring in about 2% to 10% of patients. One study found that Exparel is safe for both adults and children undergoing painful procedures.

Exparel has been used in various surgeries to help reduce pain and has been shown to lower the need for strong painkillers, like opioids, for up to 72 hours after surgery. While some side effects may occur, the treatment is considered safe for managing pain after surgery. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Exparel is unique because it delivers a long-lasting anesthetic effect directly at the surgical site, which can help manage postoperative pain more effectively than traditional options like opioids or standard local anesthetics. Researchers are excited about Exparel because it uses bupivacaine encapsulated in a lipid-based delivery system, allowing for a controlled and extended release of pain relief, potentially reducing the need for opioids. This can lead to fewer side effects and a lower risk of addiction, which is a major advantage over conventional pain management methods.

What is the effectiveness track record for Exparel in managing postoperative pain?

Research has shown that Exparel, a type of pain relief medication, has mixed results for controlling pain after surgery. Some studies indicate it does not provide better pain relief than drugs like ropivacaine or bupivacaine hydrochloride. In over 70% of trials, it did not significantly reduce pain compared to placebos or other painkillers. However, other reports highlight that patients using Exparel have experienced low pain levels and high satisfaction after surgery. Although results vary, Exparel has been effective for some patients in managing postoperative pain. Participants in this trial will receive an EXPAREL IPSA block intraoperatively to evaluate its effectiveness in postoperative pain management. ^{6 7 8 9 10}

Who Is on the Research Team?

William Mihalko, MD, PhD

Principal Investigator

Campbell Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28478185/

Effectiveness of Bupivacaine Liposome Injectable ... Conclusion: There is no benefit in the use of liposomal bupivacaine compared with ropivacaine for postoperative pain control in TKA.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022480421001244

The Efficacy of Liposomal Bupivacaine for Opioid and Pain ... Liposomal bupivacaine did not demonstrate significant pain relief compared to placebo or active agents in 74.58% of RCTs.

3. jamanetwork.com jamanetwork.com/journals/jamasurgery/fullarticle/2790975

Efficacy of Liposomal Bupivacaine and ... This study found that liposomal bupivacaine did not improve postoperative recovery or pain compared with bupivacaine hydrochloride alone among patients ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT07212114

NCT07212114 | Efficacy of EXPAREL vs. Bupivacaine The objective is to determine whether the EXPAREL-based regimen provides more effective and longer-lasting analgesia compared to bupivacaine HCl ...

5. investor.pacira.com investor.pacira.com/news-releases/news-release-details/new-data-support-benefits-exparel-postsurgical-analgesia

New Data Support the Benefits of EXPAREL for ... Results Presented at American Society for Aesthetic Plastic Surgery Meeting Show Patients Treated with EXPAREL Reported Low Pain Scores, High Satisfaction ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30521078/

Incidence of adverse events attributable to bupivacaine ... The aim of this study was to describe the incidence of local anesthetic systemic toxicity syndrome in pediatric surgical patients receiving liposomal ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/022496s9lbl.pdf

EXPAREL (bupivacaine liposome injectable suspension) The common adverse reactions (incidence greater than or equal to 2% to less than 10%) following EXPAREL administration were pyrexia, dizziness, edema ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02969187

Bupivacaine Liposomal Injection (Exparel) for Postsurgical ... The aim of this study is to study the opiate usage, pain and nausea post laparoscopic gastric bypass or sleeve gastrectomy using Exparel versus Bupivacaine as ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2468428725000784

Liposomal bupivacaine infiltration for postprocedural ... These findings suggest that LB is safe to use for postprocedural analgesia in pediatric and adult patients undergoing painful interventions for vascular ...

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

Bupivacaine Liposome (Exparel) - Medical Clinical Policy ... The authors concluded that bupivacaine extended-release demonstrated a statistically significant reduction in pain through 72 hours, decreased opioid ...