Cryoneurolysis for ACL Reconstruction

Recruiting at 1 trial location

Overseen By Sean Mc Millan, DO

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Virtua Health, Inc.

Must not be taking: Opioids

Disqualifiers: Under 14, Non-English, Reynauds, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

20 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that participants should be opioid naïve, meaning they should not be regularly using opioids before the surgery.

What data supports the effectiveness of the treatment Cryoneurolysis for ACL Reconstruction?

Research shows that ultrasound-guided cryoneurolysis, a technique using cold temperatures to target nerves, has been effective in providing pain relief after surgeries like mastectomy and thoracic surgery. Patients have reported long-term pain relief and improved function, suggesting it could be a useful option for managing pain after ACL reconstruction. ^{1 2 3 4 5}

Is cryoneurolysis generally safe for humans?

Cryoneurolysis, which uses extreme cold to treat nerve pain, is considered a safe procedure with minimal risk of complications when done with imaging guidance. Studies have shown it provides pain relief without causing permanent nerve damage, and no serious complications have been identified in patients. ^{1 2 3 6 7}

How does cryoneurolysis differ from other treatments for ACL reconstruction?

Cryoneurolysis is unique because it uses extremely cold temperatures to temporarily block pain signals by freezing the nerves, unlike other treatments that may rely on medications or physical therapy. This method is guided by ultrasound to ensure precise targeting of the nerves, potentially offering long-term pain relief without the need for drugs. ^{1 2 3 4 5}

What is the purpose of this trial?

The purpose of the research is to investigate the effect of preoperative Cryoneurolysis of the knee on postoperative pain management in patients undergoing autograft anterior cruciate ligament (ACL) reconstruction (a surgical procedure that makes a new ACL using the patient's own tendon). Cryoneurolysis is an approved process of applying extreme cold temperatures to targeted nerves in order to decrease or eliminate pain. . If you take part in the research, you will be randomly assigned (assigned by chance, like a flip of a coin) to Group A (standard care) or Group B (standard care plus Cryoneurolysis). Participants in both groups will undergo standard ACL reconstruction and receive standard preoperative and postoperative pain management. Participants in Group B only will also receive a standard treatment of Cryoneurolysis to their surgical knee within 7-10 days before their scheduled surgery. Participants in both groups (A \& B) will be asked to bring their remaining postoperative pain medication to their postoperative follow-up appointments for review by study personnel. Participants will also be asked to complete a survey about their knee activity, function and symptoms at these appointments. Your time in the study will last until the completion of the 12-week postoperative follow-up appointment.

Eligibility Criteria

This trial is for patients scheduled for ACL reconstruction using their own tendon. They must be able to undergo standard care and willing to potentially receive Cryoneurolysis before surgery. Specific eligibility criteria are not provided, but typically include being in good health with no conditions that would interfere with the study or recovery.

Inclusion Criteria

Patients who are opioid naïve

I am 14 years old or older.

I am having ACL reconstruction using my own tissue.

Exclusion Criteria

I do not speak or read English.

I am having ACL surgery using donor tissue.

Patients who consistently use opioids preoperatively

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative

Participants in Group B receive Cryoneurolysis treatment 7-10 days before surgery

1-2 weeks

1 visit (in-person)

Surgery and Immediate Post-operative Care

Participants undergo ACL reconstruction and receive standard preoperative and postoperative pain management

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness, with assessments at 1-week, 6-weeks, and 12-weeks post-surgery

12 weeks

3 visits (in-person)

Treatment Details

Interventions

• Cryoneurolysis

Trial Overview The study tests if applying extreme cold (Cryoneurolysis) to nerves around the knee before ACL surgery can reduce pain after the operation. Participants will either get standard care or standard care plus Cryoneurolysis, chosen randomly, and compare their post-surgery pain medication use.

Participant Groups

Group I: Arm B: Usual care plus pre-operative cryoneurolysis Experimental Treatment 1 Intervention

Those randomized to the intervention group (Group B) will receive a standard treatment of Cryoneurolysis to their surgical knee within 7-10 days of their scheduled surgery. Treatment nerves for the procedure will include the anterior femoral cutaneous nerve (AFCN), supra-patellar branch of the saphenous nerve (SPBSN) and infra-patellar branch of the saphenous nerve (IPBSN).

Group II: Arm A: ACL reconstruction usual care Active Control 1 Intervention

On the day of surgery, all patients (Group A and Group B) will receive a multi-modal oral pre-operative cocktail and an ultrasound guided adductor canal block. Additionally, an ultrasound guided popliteal or infiltration of the tissue plane between the popliteal artery and the capsule of the knee (iPACK) block will be administered. The pre-operative oral medication cocktail and block medications are as follows: Acetaminophen 975 mg x 1, Celecoxib 400 mg PO x 1, adductor canal block with 133 mg (10 mL) liposomal bupivacaine (EXPAREL) admixed with 0.5% bupivacaine HCl 50 mg (10 mL), popliteal or iPACK nerve infiltration with 133 mg (10 mL) liposomal bupivacaine (EXPAREL) admixed with 0.5% bupivacaine HCl 50 mg (10 mL). 15 mg IV ketorolac at conclusion of the case will be administered.

Who Is Running the Clinical Trial?

Virtua Health, Inc.

Lead Sponsor

Trials

10

Recruited

690+

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

Findings from Research

Ultrasound-guided percutaneous cryoneurolysis significantly reduced pain levels on postoperative day 2 after mastectomy, with active treatment participants reporting a median pain score of 0 compared to 3 in the sham group (P < 0.001).

The technique also led to a dramatic reduction in opioid use during the first three weeks post-surgery, with the active group using only 1.5 mg of oxycodone compared to 72 mg in the sham group, and resulted in lower rates of chronic pain after one year (3% in active vs 17% in sham, P < 0.001).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative Ultrasound-guided Percutaneous Cryoneurolysis for the Treatment of Pain after Mastectomy: A Randomized, Participant- and Observer-masked, Sham-controlled Study. Ilfeld, BM., Finneran, JJ., Swisher, MW., et al.[2023]

The size of the ice ball created during ultrasound-guided percutaneous cryoneurolysis is significantly influenced by the gauge of the cryoprobe used, with larger probes (14 gauge) producing ice balls that are up to 512% larger and achieving much lower temperatures compared to smaller probes (18 gauge).

Visualizing a nerve fully encompassed in an ice ball does not guarantee effective treatment, as temperatures within the ice ball may not reach the levels necessary to induce Wallerian degeneration, highlighting the need for further research to understand the implications for human tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative Effects of Various Factors on Ice Ball Formation and Ablation Zone Size During Ultrasound-Guided Percutaneous Cryoneurolysis: A Laboratory Investigation to Inform Clinical Practice and Future Research. Said, ET., Marsh-Armstrong, BP., Fischer, SJ., et al.[2023]

Ultrasound guidance during cryoneurolysis allows for real-time monitoring of needle placement, leading to more accurate targeting of peripheral nerves and improved outcomes in pain relief.

Patients have reported varying degrees of long-term pain relief and functional improvement from cryoneurolysis, with no serious complications noted, suggesting it is a safe alternative to other pain management techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-Guided Cryoanalgesia of Peripheral Nerve Lesions. Djebbar, S., Rossi, IM., Adler, RS.[2017]

Ultrasound-guided percutaneous cryoanalgesia effectively targets intercostal nerves to provide postoperative pain relief after thoracic surgery, which is crucial for improving lung function and reducing complications.

Using a high-frequency ultrasound probe allows for precise placement of the cryoprobe near the intercostal nerve, confirmed by specific ultrasound signs, enhancing the efficacy of the cryoanalgesia technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short communication: ultrasound-guided percutaneous cryoanalgesia of intercostal nerves for uniportal video-assisted thoracic surgery. Nicolás, M., Acosta, CM., Martinez Ferro, M., et al.[2022]

Ultrasound-guided cryoablation of intercostal nerves has been successfully performed in four patients with postthoracotomy pain syndrome, providing pain relief for at least one month without any complications.

The use of ultrasound enhances the safety of the procedure by allowing visualization of the pleura, which is particularly beneficial in thin patients, potentially reducing the risk of pneumothorax and improving the success rate of cryoablation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-guided intercostal nerve cryoablation. Byas-Smith, MG., Gulati, A.[2016]

Cryoanalgesia, or cryoneurolysis, is a safe and effective method for relieving pain by applying extreme cold to peripheral nerves, interrupting pain signals without causing permanent nerve damage.

This technique, guided by imaging methods like ultrasound or CT, offers a minimally invasive alternative to traditional pain management approaches, especially important in the context of the opioid crisis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous cryoanalgesia for pain palliation: Current status and future trends. Filippiadis, D., Efthymiou, E., Tsochatzis, A., et al.[2021]

In a study involving 113 patients undergoing ultrasound-guided percutaneous cryoneurolysis for spasticity, 96.75% of nerve treatments resulted in no significant pain or dysesthesias beyond the treatment period, indicating a high safety profile.

While a few patients experienced temporary nerve pain or numbness, most adverse effects were manageable and resolved within three months, suggesting that cryoneurolysis could be a safe and effective treatment option for spasticity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Adverse Effects of Cryoneurolysis for the Treatment of Spasticity. Winston, P., MacRae, F., Rajapakshe, S., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Preoperative Ultrasound-guided Percutaneous Cryoneurolysis for the Treatment of Pain after Mastectomy: A Randomized, Participant- and Observer-masked, Sham-controlled Study. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Relative Effects of Various Factors on Ice Ball Formation and Ablation Zone Size During Ultrasound-Guided Percutaneous Cryoneurolysis: A Laboratory Investigation to Inform Clinical Practice and Future Research. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Ultrasound-Guided Cryoanalgesia of Peripheral Nerve Lesions. [2017]

4. Italy pubmed.ncbi.nlm.nih.gov

Short communication: ultrasound-guided percutaneous cryoanalgesia of intercostal nerves for uniportal video-assisted thoracic surgery. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Ultrasound-guided intercostal nerve cryoablation. [2016]

6. France pubmed.ncbi.nlm.nih.gov

Percutaneous cryoanalgesia for pain palliation: Current status and future trends. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Analysis of Adverse Effects of Cryoneurolysis for the Treatment of Spasticity. [2023]