Pain Management for Postoperative Pain

Overseen By Debbi Warren, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Foundation for Orthopaedic Research and Education

Must not be taking: Opioids, Local anesthetics

Disqualifiers: Pregnancy, Previous lumbar surgery, 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: 14

Duration: 0-72 hours post-operatively

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods to manage pain after transforaminal lumbar interbody fusion, a type of back surgery. It compares a pain relief injection called Exparel (bupivacaine liposome injectable suspension) with standard treatment using Bupivacaine. Researchers aim to determine which option better reduces pain, decreases the need for narcotics, shortens hospital stays, and helps patients begin physical therapy sooner. Individuals who have undergone this type of back surgery and are not allergic to common pain medications may be suitable for the trial. As a Phase 2, Phase 3 trial, this study evaluates the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in pain management.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you use opioids regularly, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Exparel is generally well-tolerated. In studies, common side effects included fever, dizziness, and swelling, affecting 2% to 10% of patients. These side effects are usually mild. Exparel also reduces pain and lessens the need for opioids for up to 72 hours after surgery. However, caution is advised when injecting Exparel into joints or the spine, as it can be harmful. Overall, these findings suggest that Exparel is safe for managing post-surgical pain in both adults and children. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for postoperative pain?

Exparel is unique because it combines the local anesthetic bupivacaine with a delivery system called DepoFoam, which allows for a slow and sustained release of the medication. This can potentially provide longer-lasting pain relief compared to standard bupivacaine injections, which are commonly used for postoperative pain management. Researchers are excited about Exparel because it may reduce the need for opioids after surgery, offering a safer and more effective pain control option.

What evidence suggests that this trial's treatments could be effective for postoperative pain management?

This trial will compare Exparel, a special form of the pain reliever bupivacaine, with standard bupivacaine for managing postoperative pain. Research has shown mixed results for Exparel in managing pain after surgery. Many studies indicate it doesn't significantly reduce pain more than standard treatments like regular bupivacaine. For instance, one study found no improvement in pain control or recovery when using Exparel compared to bupivacaine alone. Although Exparel is designed to provide longer-lasting pain relief, it often does not outperform traditional treatments in most trials. So far, evidence suggests Exparel may not be more effective than standard pain management options in many cases. ^{3 6 7 8 9}

Who Is on the Research Team?

John Small, MD

Principal Investigator

Florida Orthopaedic Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are having a specific back surgery (1-3 level TLIF) and have a BMI between 18-35. They must not be pregnant, allergic to pain meds or local anesthetics, have had previous lumbar surgery, take high doses of opioids, or have muscle disorders like myasthenia gravis.

Inclusion Criteria

I am admitted for a 1-3 level spinal fusion surgery.

Patients who have given written informed consent

BMI between 18-35 kg/m2

Exclusion Criteria

I am currently pregnant.

Patients with known allergy to local anesthetics

Patients with known allergic reactions to standard of care analgesics

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Exparel TLIP Injection or Bupivacaine HCl TLIP Injection during surgery

0-72 hours post-operatively

In-hospital stay

Follow-up

Participants are monitored for pain intensity, opioid consumption, and physical therapy progress

14 days

First clinic visit at 14 days post-operatively

What Are the Treatments Tested in This Trial?

Interventions

• Bupivacaine
• Exparel

Trial Overview The study compares two types of pain relief after back surgery: Exparel versus standard Bupivacaine. It aims to see if Exparel can better reduce pain, cut down on the need for narcotics, shorten hospital stays, and help patients get moving sooner.

How Is the Trial Designed?

Group I: Exparel TLIP Injection Experimental Treatment 1 Intervention

Subjects will receive 20 mL of EXPAREL 266mg mixed with 10 mL of 0.25% bupivacaine. A total of 30 mL of mixed solution is injected into the thoracolumbar interfacial plane.

Group II: Bupivicaine HCL TLIP Injection Active Control 1 Intervention

Standard of care will consist of 0.25% Bupivacaine HCl TLIP injection. Subjects will receive 30 mL of the solution, injected into the thoracolumbar interfacial plane.

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?

Foundation for Orthopaedic Research and Education

Lead Sponsor

Trials

16

Recruited

1,000+

Pacira Pharmaceuticals, Inc

Industry Sponsor

Trials

142

Recruited

14,300+

Headquarters

Tampa, USA

Known For

Non-opioid Pain Management

Top Products

Exparel, Zilretta, iovera

Dr. Jonathan Slonin

Pacira Pharmaceuticals, Inc

Chief Medical Officer since 2020

BSc in Biomedical Engineering and MD from University of Miami, MBA from George Washington University

Frank D. Lee

Pacira Pharmaceuticals, Inc

Chief Executive Officer since 2024

BSc in Chemical Engineering from Vanderbilt University, MBA from Wharton Graduate School of Business

Published Research Related to This Trial

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 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 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]

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]

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 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 100 patients with pulpal necrosis, liposomal bupivacaine did not show a statistically significant improvement in postoperative pain relief compared to standard bupivacaine, with success rates of 29% and 22% respectively.

While liposomal bupivacaine had some effects on soft tissue numbness and non-narcotic medication use, these effects were not clinically significant, indicating that it may not provide additional benefits over traditional bupivacaine for postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Liposomal Bupivacaine (Exparel) Significantly Reduce Postoperative Pain/Numbness in Symptomatic Teeth with a Diagnosis of Necrosis? A Prospective, Randomized, Double-blind Trial. Glenn, B., Drum, M., Reader, A., et al.[2017]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3772762/

Liposomal extended-release bupivacaine for postsurgical ... Bupivacaine liposome injectable suspension​​ Due to its novel design and slow release, EXPAREL® can produce local analgesia for up to 72 hours,12 about ten times ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2777506

Standard vs Liposomal Bupivacaine for Postoperative Pain ... Liposomal bupivacaine did not provide improved pain control and did not reduce adjunctive opioid use compared with conventional bupivacaine formulation over 3 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11975001/

Real-World Pharmacovigilance Analysis of Adverse Events ... This study analyzed adverse events (AEs) associated with liposomal bupivacaine and bupivacaine using the FDA Adverse Event Reporting System (FAERS) database

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. 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 ...

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 ...