Pain Management After VATS for Postoperative Pain

Overseen By Yatish Ranganath, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Nada Sadek

Disqualifiers: Chronic pain, Opioid tolerance, Hepatic disease, 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: 1

Duration: Immediate post-operative period

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to identify the best method for managing pain after video-assisted thoracoscopic surgery (VATS), a minimally invasive chest surgery. Although VATS is less invasive than open surgery, many patients still experience significant pain afterward. The study compares two pain treatments: liposomal bupivacaine, a long-acting local anesthetic applied during surgery, and regular bupivacaine, a local anesthetic administered before surgery. The trial seeks adults scheduled for VATS who do not have chronic pain or conditions like fibromyalgia and are not accustomed to taking opioids regularly. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have chronic pain or are opioid-tolerant, you may not be eligible to participate.

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

Research shows that liposomal bupivacaine, used to manage post-surgical pain, is generally safe. Studies have found its safety profile similar to regular bupivacaine across various surgeries, with comparable types and numbers of side effects. One study demonstrated that liposomal bupivacaine was safe and effective for pain relief in patients undergoing thoracoscopic surgery, which involves small incisions and a camera.

Regular bupivacaine, also under investigation, has long been used for pain management. It is well-known and generally well-tolerated.

Both treatments in this trial have been used in other contexts and have shown safety for most patients. While side effects can occur, they are usually not severe. This trial aims to determine how well each treatment manages pain after VATS surgery. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for postoperative pain management after VATS because they offer innovative delivery methods. Liposomal bupivacaine stands out due to its use in an intercostal nerve block administered with thoracoscopic guidance, which may provide prolonged pain relief by releasing the anesthetic slowly over time. On the other hand, bupivacaine is used in a paravertebral block, a more traditional approach, but it’s guided by ultrasound for precision. These methods aim to enhance pain control, reduce reliance on opioids, and improve recovery experiences for patients.

What evidence suggests that this trial's treatments could be effective for managing post-VATS-related pain?

This trial will compare liposomal bupivacaine and bupivacaine for managing postoperative pain. Research has shown that liposomal bupivacaine often does not relieve pain more effectively than other treatments. Many studies found it did not significantly reduce pain compared to a placebo or other pain medications. However, bupivacaine, which participants in this trial may receive, has proven effective in alleviating postoperative pain. Studies have found that bupivacaine can lessen pain and reduce the need for additional painkillers after surgery. Both treatments aim to manage pain, but current evidence suggests that regular bupivacaine might be more effective. ^{6 7 8 9 10}

Who Is on the Research Team?

Nada Sadek, MD

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 undergoing VATS who are not pregnant, have a BMI under 40, and can consent. It excludes those with chronic pain conditions, opioid tolerance, allergies to study drugs, infectious diseases, coagulation issues, severe liver disease or incarceration.

Inclusion Criteria

I am scheduled for a minimally invasive chest surgery.

You weigh less than 40 times your height in kilograms.

Exclusion Criteria

I have severe liver disease.

My blood does not clot properly.

I have long-term chronic pain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either an intercostal nerve block with liposomal bupivacaine or a paravertebral block with plain bupivacaine

Immediate post-operative period

1 visit (in-person)

Post-operative Monitoring

Participants are monitored for post-operative pain, opioid usage, and lung function

Up to 72 hours post procedure

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pain scores and opioid consumption

Up to 6 months post procedure

What Are the Treatments Tested in This Trial?

Interventions

• Bupivacaine
• Liposomal bupivacaine

Trial Overview

The study tests two types of pain management medications after VATS: Bupivacaine and Liposomal bupivacaine. The aim is to determine which provides better post-surgical pain relief without causing respiratory problems.

How Is the Trial Designed?

Group I: Liposomal bupivacaine Experimental Treatment 1 Intervention

The patient will receive an intercostal nerve block by the surgeon in the operating room after anesthetic has been administered. The surgeon will use thoracoscopic guidance to administer the intercostal nerve block. The medication used in this block will liposomal bupivacaine (Exparel).

Group II: Bupivacaine Active Control 1 Intervention

The patient will receive a paravertebral block by the anesthesiologist staffing the pain service area within the hospital prior to surgery. This regional anesthesia will be done using ultrasound guidance. The medication used in this block will be plain bupivacaine with epinephrine.

Who Is Running the Clinical Trial?

Nada Sadek

Lead Sponsor

Trials

1

Recruited

180+

YATISH SIDDAPURA RANGANATH

Lead Sponsor

Trials

2

Recruited

300+

Rakesh Sondekoppam Vijayashankar

Lead Sponsor

Trials

2

Recruited

320+

American Society of Regional Anesthesia

Collaborator

Trials

5

Recruited

310+

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 of 50 patients undergoing vaginal reconstructive surgery, liposomal bupivacaine (LB) did not show any significant advantage over plain bupivacaine in terms of postoperative pain control, narcotic use, or length of hospital stay.

Despite LB's higher cost, the results indicate that it is not more effective than plain bupivacaine for managing pain after surgery, suggesting a need for further research to find the best pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal versus plain bupivacaine for pain control following vaginal reconstruction. Jensen, S., Amasyali, AS., Keheila, M., et al.[2023]

In a study of 20 patients undergoing lingual nerve microsurgery, those who received liposomal bupivacaine (LB) reported significantly less postoperative pain and consumed fewer opioid pills compared to those who received bupivacaine hydrochloride (BH).

The findings suggest that LB, with its prolonged duration of action, is more effective in reducing postoperative pain and opioid consumption, supporting its use in surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal bupivacaine use in exploratory lingual nerve microsurgery: does liposomal bupivacaine use decrease postoperative pain and opioid consumption compared to bupivacaine hydrochloride? A pilot study. Jacobus, D., Mehr, S., Ziccardi, V.[2021]

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 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]

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 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]

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 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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4970774/

Local bupivacaine for postoperative pain management in ...

Intraoperative local bupivacaine application is effective in decreasing postoperative pain in patients with thyroidectomy.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7002882/

Effect of bupivacaine on postoperative pain and analgesics ...

This study sought to verify the efficacy of bupivacaine on postoperative pain and analgesics use after single-incision laparoscopic appendectomy (SILA). Methods.

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S2949962325000105

Comparing intraoperative administration of long-acting ...

This study compared postoperative pain outcomes with LB versus MCs such as ropivacaine-epinephrine-clonidine-ketorolac, bupivacaine-epinephrine-dexamethasone, ...

4.

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 ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06531603

Postoperative Analgesic Effectiveness of Bupivacaine With ...

Postoperative Analgesic Effectiveness of Bupivacaine With and Without Dexmedetomidine in Patients With Abdominal Surgery. ClinicalTrials.gov ID NCT06531603.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11045961/

Effect of liposomal bupivacaine for preoperative erector ...

Liposomal bupivacaine has been shown to provide postsurgical analgesia with a similar safety profile to bupivacaine HCl in a variety of surgical scenarios, such ...

7.

cdn.clinicaltrials.gov

cdn.clinicaltrials.gov/large-docs/47/NCT04559347/Prot_000.pdf

Title : Single Shot Liposomal Bupivacaine (EXPAREL®)/ ...

The general objectives of this proposed investigation are to establish the incidence of adverse events in patients receiving a Single Shot ...

8.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0003497518311676

A Randomized Controlled Trial of Liposomal Bupivacaine ...

This prospective, randomized, double-blind study examines the efficacy of Exparel as a novel single-dose application parasternal nerve block in postoperative ...

9.

annalsthoracicsurgery.org

annalsthoracicsurgery.org/article/S0003-4975(22)00350-2/fulltext

Randomized Trial of Bupivacaine Versus Liposomal ...

The objective of this single-blind randomized study is to compare local infiltration of bupivacaine or liposomal bupivacaine (LipoB) in narcotic naïve patients.

10.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12267960/

Efficacy and Safety of Bupivacaine Liposomal in Intercostal ...

Conclusion: LB is safe and effective for ICNB, providing significant postoperative pain relief for patients undergoing uniportal thoracoscopic surgery. Trial ...