Liposomal Bupivacaine for Postoperative Pain

(SOOOTHE Trial)

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Missouri, Kansas City

Must not be taking: Opioids, NSAIDs

Disqualifiers: Opioid use disorder, Cardiovascular disease, Liver disorder, Renal disease, others

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

Compensation: Varies

Number of Visits: 13

Duration: 7 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to manage pain after a C-section using a special form of bupivacaine, a numbing medicine, to reduce opioid use. The treatment involves an abdominal injection to block pain, potentially providing relief for up to 96 hours. The goal is to determine if this method can help reduce opioid use after surgery. Women scheduled for a planned C-section, who can communicate about their pain, might be suitable for this trial. As a Phase 4 trial, this research aims to understand how this already FDA-approved and effective treatment can benefit more patients.

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

The trial information does not specify if you need to stop taking your current medications. However, if you are currently using opioids or have a history of opioid use disorder, you would not be eligible to participate.

What is the safety track record for these treatments?

Research has shown that liposomal bupivacaine, also known as EXPAREL®, is generally safe for patients. In various studies, most participants did not experience serious side effects. Common mild reactions included fever, dizziness, and some swelling, affecting less than 10% of patients.

While the FDA has approved liposomal bupivacaine for pain management in certain surgeries, studies have produced mixed results regarding its effectiveness compared to other pain treatments. Some research found it did not always control pain better than standard bupivacaine or reduce the need for additional opioids. However, it can relieve pain for up to 96 hours, which is longer than regular bupivacaine.

Overall, the treatment appears safe, but its effectiveness may vary. This information is important to consider when deciding whether to join a trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about liposomal bupivacaine for postoperative pain because it offers a longer-lasting pain relief compared to standard treatments. Unlike traditional local anesthetics that may wear off in a few hours, liposomal bupivacaine uses a lipid-based delivery system that slowly releases the medication, extending its effect for up to 96 hours. This can mean fewer doses and potentially less reliance on opioids for pain management, which is a significant advantage in enhancing patient comfort and safety after surgery.

What evidence suggests that liposomal bupivacaine is effective for reducing postoperative pain?

Research has shown that liposomal bupivacaine, a long-lasting form of a local painkiller, produces mixed results for managing post-surgery pain. In this trial, participants will receive either liposomal bupivacaine or a placebo. Studies often find that liposomal bupivacaine does not provide better pain relief than other treatments or a placebo. In many trials, it did not significantly reduce pain or aid recovery more than other pain relief methods. Some research also found it was not clearly superior to standard bupivacaine, a common painkiller. Overall, while liposomal bupivacaine is designed to last longer, the evidence does not consistently show it works better for post-surgery pain. ^{1 2 6 7 8}

Who Is on the Research Team?

Gary Sutkin, MD

Principal Investigator

University of Missouri, Kansas City

Devika Maulik, MD

Principal Investigator

Children's Mercy Hospital Kansas City

Are You a Good Fit for This Trial?

This trial is for women aged 18-45 having a scheduled cesarean delivery, who can communicate in English or with an interpreter. They must be able to do pain assessments and haven't used opioids recently. It's not for those with unscheduled deliveries, opioid use disorder, certain health issues like severe kidney disease, allergies to local anesthetics/NSAIDs, or complications requiring additional surgery.

Inclusion Criteria

Ability to complete numeric pain scale assessment and surveys

I need an interpreter to communicate in English.

I am scheduled for a cesarean delivery without complications.

Exclusion Criteria

Deliveries that were not scheduled in advance.

I have kidney problems or my creatinine level is above 1.1.

You were born before 37 weeks of pregnancy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a transversus abdominis plane block with either liposomal bupivacaine or saline during cesarean delivery

7 days

Inpatient stay up to 6 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of pain, opioid use, and recovery quality

6 weeks

Postoperative visits at 7 days, 14 days, and 6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Deposition of saline
• Liposomal bupivacaine
• TAP block

Trial Overview

The study tests if a TAP block using liposomal bupivacaine reduces the need for opioid painkillers after C-sections through day 7 post-op. It's a double-blind trial where patients are randomly assigned to receive either the drug or saline as control without knowing which one they get.

How Is the Trial Designed?

Group I: Treatment Active Control 2 Interventions

The transversus abdominis plane block is a procedure involving injection of a local anesthetic solution into the abdominal plane between the internal oblique muscle and the transversus abdominis muscle. In our institution, this is done under ultrasound guidance which is the current standard to improve efficacy and limit complications. Liposomal bupivacaine uses an innovative technology consisting of lipid-based particles containing active pharmaceutical agent (bupivacaine) which extends the duration of the medication through a process of gradual release for metabolism.This drug delivery technology extends the duration of action to up to 96 hours when given at a dose of 266 mg liposomal bupivacaine admixed with 30 ml of bupivacaine 0.25% and 30 ml of saline. Forty ml of solution is deposited on the left side of the abdomen and 40 ml on the right.

Group II: Control Placebo Group 2 Interventions

The transversus abdominis plane block will be performed under ultrasound guidance with deposition of 80 ml of saline (40 ml on either side).

Who Is Running the Clinical Trial?

University of Missouri, Kansas City

Lead Sponsor

Trials

73

Recruited

34,600+

Truman Medical Center

Collaborator

Trials

10

Recruited

301,000+

Published Research Related to This Trial

Transversus abdominis plane (TAP) blocks with liposomal bupivacaine provided pain relief at rest that was non-inferior to epidural analgesia in patients recovering from major abdominal surgery, with a minimal difference in pain scores.

However, patients receiving TAP blocks required more opioids than those with epidurals, but experienced significantly less hypotension, suggesting TAP blocks may be safer for patients at risk of low blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transversus abdominis plane block with liposomal bupivacaine versus continuous epidural analgesia for major abdominal surgery: The EXPLANE randomized trial. Turan, A., Cohen, B., Elsharkawy, H., et al.[2022]

A case report highlights a significant safety concern regarding the use of liposomal bupivacaine in transversus abdominis plane (TAP) blocks, as an elderly patient experienced postoperative respiratory depression after surgery.

This incident raises questions about the pharmacokinetics and safety of liposomal bupivacaine, especially when used alongside intravenous opioids and other analgesics in multimodal pain management after open abdominal surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed Respiratory Depression Secondary to Opioid Overdose After Multimodal Analgesia With Transversus Abdominis Plane Blocks in Postanesthesia Care Unit: A Case Report. O'Rourke, M., Schmidt, ES., Metry, JE., et al.[2021]

In a study of 100 patients undergoing elective laparoscopic colectomy, those receiving liposomal bupivacaine TAP blocks required significantly less narcotic medication (5.06 mg) compared to those receiving standard bupivacaine (18.75 mg), indicating better pain management.

Patients treated with liposomal bupivacaine also experienced earlier bowel function (1.7 days vs 2.4 days) and shorter hospital stays (2.7 days vs 3.4 days), suggesting improved postoperative recovery outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transversus Abdominis Plane Blocks in Laparoscopic Colorectal Surgery: Better Pain Control and Patient Outcomes with Liposomal Bupivacaine than Bupivacaine. Guerra, L., Philip, S., Lax, EA., et al.[2020]

Liposomal bupivacaine (LB) used in a transversus abdominis plane (TAP) block, either alone or with intrathecal morphine (ITM), resulted in similar opioid consumption compared to ITM alone for pain management after cesarean delivery, indicating its effectiveness as an analgesic option.

Both LB groups experienced significantly less pruritus (itchiness) compared to the ITM group, suggesting that LB may offer a safer profile with fewer side effects in postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of transversus abdominis plane block with liposomal bupivacaine after cesarean delivery with or without intrathecal morphine. Habib, AS., Nedeljkovic, SS., Horn, JL., et al.[2022]

In a study involving patients undergoing robot-assisted hysterectomy, the use of liposomal bupivacaine in subcostal TAP blocks significantly reduced total opioid use in the first 72 hours post-surgery compared to standard bupivacaine.

Patients receiving liposomal bupivacaine reported lower maximum pain scores and had a decreased incidence of nausea and vomiting, suggesting improved overall satisfaction and comfort after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound guided subcostal transversus abdominis plane (TAP) infiltration with liposomal bupivacaine for patients undergoing robotic assisted hysterectomy: A prospective randomized controlled study. Hutchins, J., Delaney, D., Vogel, RI., et al.[2022]

In a randomized controlled trial involving 57 patients undergoing midurethral sling placement, liposomal bupivacaine resulted in lower median pain scores on postoperative day 1 compared to a mixture of bupivacaine and lidocaine (20 mm vs 30 mm), indicating some efficacy in pain management.

Despite the initial lower pain scores, there were no significant differences in overall opioid and nonsteroidal anti-inflammatory drug consumption or in quality of recovery scores after 7 days, suggesting that liposomal bupivacaine may not provide a clinically significant advantage over traditional pain management methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal Bupivacaine Versus Bupivacaine Hydrochloride with Lidocaine during Midurethral Sling Placement: A Randomized Controlled Trial. Iwanoff, C., Salamon, C.[2020]

Citations

1.

pmc.ncbi.nlm.nih.gov

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

Liposomal extended-release bupivacaine for postsurgical ...

In this brief review, we provide an update of the current knowledge in the use of bupivacaine for postsurgical analgesia. Keywords: bupivacaine, liposome, ...

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.

pubmed.ncbi.nlm.nih.gov

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

Effectiveness of Bupivacaine Liposome Injectable ...

There is no benefit in the use of liposomal bupivacaine compared with ropivacaine for postoperative pain control in TKA.

4.

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 ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03001453

NCT03001453 | Intraoperative Liposomal Bupivacaine vs. ...

The purpose of this study is to compare two medications currently injected intra-operatively to help decrease pain after surgery in patients undergoing a ...

6.

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 ...

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 peripheral ...

8.

aetna.com

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

Bupivacaine Liposome (Exparel) - Medical Clinical Policy ...

The authors concluded that liposome bupivacaine added to standard bupivacaine may lower pain and enhance patient's satisfaction in the first postoperative week ...