Pain Control Methods for Ankle Surgery

(PvP Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Campbell Clinic

Must not be taking: Injectable anesthetics, Narcotics

Disqualifiers: Chronic pain, Peripheral neuropathy, 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: 3

Duration: Immediate perioperative period

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods to control pain after ankle or hindfoot surgery. One group receives Exparel (bupivacaine liposome injectable suspension) mixed with bupivacaine, injected directly around the joint area post-surgery. The other group receives a popliteal block, a nerve block with bupivacaine administered before surgery to numb the area. Individuals scheduled for ankle or hindfoot surgery at Campbell Surgery Center, who do not have chronic pain or certain allergies, might be suitable for this study. As a Phase 4 trial, this study involves an FDA-approved treatment and 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, but it excludes those with long-term narcotic use. It's best to discuss your specific medications with the trial coordinators.

What is the safety track record for these treatments?

Research shows that the treatments under study, Exparel and bupivacaine, are generally well-tolerated. Studies indicate that Exparel does not cause serious side effects such as heart problems or delayed wound healing. This long-lasting form of bupivacaine is injected directly into the surgery area to manage pain.

Research suggests that the bupivacaine popliteal block, a type of local anesthesia, is usually safe with few major complications. However, using a large dose could rarely lead to issues like infection or bleeding. Both treatments are already used for pain control, indicating a strong safety record.

These findings suggest that both treatments are considered safe for use in humans, especially since they are being tested in a Phase 4 trial. This phase typically means they have been approved for other uses and are being further studied for specific purposes. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for ankle surgery pain control because they offer innovative pain management techniques. The periarticular injection combines Exparel and bupivacaine, allowing for targeted pain relief directly at the surgical site, potentially reducing the need for systemic pain medications. On the other hand, the popliteal block uses an ultrasound-guided injection of bupivacaine, providing nerve block pain relief before surgery even begins. Both methods aim to improve comfort and recovery time by offering precise, localized pain management compared to traditional oral or systemic analgesics.

What evidence suggests that this trial's treatments could be effective for pain control after ankle surgery?

In this trial, participants will receive one of two pain control methods following ankle surgery. Studies have shown that Exparel, a long-lasting form of bupivacaine, effectively manages pain after foot and ankle surgeries. Research indicates that Exparel reduces the need for opioid painkillers, offering a significant benefit. Participants in the Periarticular Injection arm will receive Exparel mixed with bupivacaine.

Participants in the Popliteal Block arm will receive a popliteal block using bupivacaine, a method also effective in reducing post-surgery pain. This method has been linked to a decreased need for additional pain medications after surgery. Both treatments are well-supported by evidence for easing pain following ankle surgeries, making them reliable options. ^{5 6 7 8 9}

Who Is on the Research Team?

Garnett A Murphy, MD

Principal Investigator

Campbell Clinic

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 who need foot or ankle surgery and can follow the study plan, including all visits. They must be healthy enough for surgery (ASA I-III), speak English, and have their operation at Campbell Surgery Center. People with diabetes must have an Hbg A1C of 7 mg/dl or less. Those with chronic pain conditions, peripheral neuropathy, long-term narcotic use, or allergies to certain anesthetics cannot join.

Inclusion Criteria

My surgery is scheduled at Campbell Surgery Center in Germantown, TN.

I have had surgery to correct bone structure in my ankle or to repair a broken ankle.

ASA I-III with medical clearances as needed

Exclusion Criteria

You have been taking strong painkillers for a long time before the surgery.

I have been diagnosed with chronic pain syndrome.

Hbg A1C is > 7 mg/dl in diabetic patients only

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a periarticular injection or a popliteal block for pain control during ankle or hindfoot surgery

Immediate perioperative period

1 visit (in-person)

Follow-up

Participants are monitored for pain control and medication use post-surgery

12 weeks

Multiple visits (in-person and virtual) at weeks 2, 6, and 12

What Are the Treatments Tested in This Trial?

Interventions

• Bupivicaine
• Exparel

Trial Overview The study compares two pain control methods after foot or ankle bone surgery: a periarticular injection using Exparel versus a popliteal block with Bupivicaine. The goal is to see which one is more effective and safer for managing post-surgery pain.

How Is the Trial Designed?

Group I: Periarticular Injection Active Control 1 Intervention

Subjects undergoing hindfoot osteotomy or fusion, ankle osteotomy or fusion, or ankle fracture repair will recieve a periarticular injection by the surgeon using 10 milliliters of Exparel mixed with 10 milliliters of bupivicaine 0.5 percent at the end of the procedure.

Group II: Popliteal Block Active Control 1 Intervention

Subjects undergoing hindfoot osteotomy or fusion, ankle osteotomy or fusion, or ankle fracture repair will recieve a popliteal block by the anesthesiologist using 30 milliliters of bupivicaine 0.5 percent in the pre-operative area, prior to surgery, using an ultrasound machine for guidance.

Who Is Running the Clinical Trial?

Campbell Clinic

Lead Sponsor

Trials

15

Recruited

2,100+

Published Research Related to This Trial

DepoFoam bupivacaine, an extended-release formulation of the local anesthetic bupivacaine, provides effective pain relief for 3-4 days after a single administration at the surgical site, reducing the need for opioid pain relief.

The safety profile of DepoFoam bupivacaine is comparable to traditional bupivacaine HCl, with adverse events being dose-related, indicating it is a safe option for managing postsurgical pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of DepoFoam(®) bupivacaine for the treatment of postsurgical pain. Bergese, SD., Onel, E., Portillo, J.[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]

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]

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 59 patients undergoing total knee arthroplasty, liposomal bupivacaine did not show a significant clinical advantage over standard bupivacaine in terms of postoperative recovery, as measured by the number of physical therapy sessions needed for discharge.

The use of liposomal bupivacaine was associated with higher medication charges, raising concerns about its cost-effectiveness compared to standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal Bupivacaine Versus Standard Periarticular Injection in Total Knee Arthroplasty With Regional Anesthesia: A Prospective Randomized Controlled Trial. Hyland, SJ., Deliberato, DG., Fada, RA., et al.[2019]

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]

EXPAREL® (bupivacaine liposome injectable suspension) provides effective pain relief for up to 72 hours after foot and ankle surgeries, making it a valuable option for outpatient procedures.

In two case studies involving complex surgeries, both patients experienced excellent control of postsurgical pain, highlighting the efficacy of EXPAREL® in managing pain without the risks associated with more extensive nerve blocks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local infiltration of liposome bupivacaine in foot and ankle surgery: case-based reviews. Herbst, SA.[2014]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40916868/

Efficacy of Liposomal Bupivacaine in Ultrasound-Guided ... Conclusion: US-guided peripheral nerve blocks using liposomal bupivacaine were associated with reduced postoperative opioid consumption and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10748683/

Efficacy of Liposomal Bupivacaine in Managing ... In this study, we compare local LB infiltration with LB used in peripheral nerve blocks in the lower extremity and compare both of these ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0949265824000046

Analgesic effectiveness of continuous versus single- ... The most important finding of this study is that cACB is better than sACB in terms of postoperative pain control 12 h after surgery and in patient satisfaction.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03696199

Randomized Controlled Trial for Ankle Fracture Pain Control This study is a multicenter, three armed, prospective randomized control trial studying the effect of a long-acting local anesthetic "cocktail" in patients ...

5. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/10711007251359634

Efficacy of Liposomal Bupivacaine in Ultrasound-Guided ... Conclusion: US-guided peripheral nerve blocks using liposomal bupivacaine were associated with reduced postoperative opioid consumption and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12028960/

Efficacy and Safety of Different Local Anesthesia ... Local anesthesia techniques are effective in reducing pain in podiatric procedures. The safety of these techniques is high, with few serious complications.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02072135

Study Details | NCT02072135 | Exparel and Ankle Surgery However, administering a large dose of bupivacaine for nerve blockade has been reported to lead to complications such as infection, hematoma, vascular puncture, ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04575688

NCT04575688 | Periarticular Injection Versus Popliteal Block This study aims to determine the effectiveness and safety of two standard of care perioperative procedures for controlling pain following ankle and hindfoot ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5623423/

AnAnkle Trial study protocol: a randomised trial comparing ... We present an ongoing randomised study aiming to compare primary PNB anaesthesia with spinal anaesthesia for ankle fracture surgery regarding ...