Cryoneurolysis for Rib Fracture Pain

Recruiting at 6 trial locations

Overseen By Brian Ilfeld, MD, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Diego

Must not be taking: Anticoagulants, Chronic opioids

Disqualifiers: Pulmonary disease, Neurologic deficit, Insulin-dependent diabetes, 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: 1

Duration: 1 day

120 Participants Needed

Trial Summary

What is the purpose of this trial?

Thoracic trauma frequently involve rib fractures which can be very painful for 2-3 months. Unfortunately, pain is not simply a "symptom" of the injuries, but a significant cause of additional medical problems: pain causes people to breath and cough less deeply/often which increases the risk of collapsing little parts of the lung. These collapsed areas often lead to complications which can increase the risk of death. In addition, the higher the amount of pain in the weeks following the fracture, the higher the risk of developing persistent, chronic pain that can last indefinitely. So, providing excellent pain control is very important for a variety of reasons. Various nerve blocks can greatly decrease pain, but even the longest acting are measured in hours or days, and not the weeks and months for which rib fracture pain can last. Therefore, opioids-"narcotics"-are the most common pain control method provided to patients; but they frequently do not provide enough pain control, have undesirable side effects like nausea and vomiting, and are sometimes misused which can lead to addiction or overdose. A prolonged nerve block lasting multiple months from a single treatment may be provided by freezing the nerve using a process called "cryoneurolysis". With cryoneurolysis and ultrasound machines, a very small "probe" may be placed through anesthetized skin and guided to the target nerve to allow freezing. The procedure takes about 5 minutes for each nerve, involves little discomfort, has no side effects, and cannot be misused or addictive. After 2-3 months, the nerve returns to normal functioning. The investigators have completed a small study suggesting that a single cryoneurolysis treatment provides potent short- and long-term pain relief following thoracic trauma with rib fractures. The ultimate objective of the proposed research is to determine if percutaneous cryoneurolysis is an effective non-opioid, single-application treatment for pain following traumatic rib fracture. The current project is a pragmatic, multicenter, randomized, triple-masked (investigators, participants, statisticians), sham/placebo-controlled, parallel-arm, human-subjects, post-market clinical trial to determine if cryoneurolysis is an effective non-opioid treatment for pain following traumatic rib fractures.

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

The trial does not specify if you need to stop taking your current medications, but it excludes those with chronic opioid use and certain conditions like anticoagulation or insulin-dependent diabetes. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Cryoneurolysis for rib fracture pain?

Research shows that intercostal nerve cryoablation, a form of cryoneurolysis, can help control pain, reduce the need for opioids, and shorten hospital stays for patients with rib fractures. Additionally, ultrasound-guided cryoanalgesia has been effective in providing pain relief after thoracic surgeries. ^{1 2 3 4 5}

Is cryoneurolysis safe for treating rib fracture pain?

Cryoneurolysis, used for rib fracture pain and other conditions, has been shown to be safe in studies, with no immediate or long-term complications reported. It is a technique that uses very low temperatures to target nerves and has been performed successfully without complications in various cases. ^{1 2 3 5 6}

How is the treatment Cryoneurolysis for rib fracture pain different from other treatments?

Cryoneurolysis is unique because it uses extremely low temperatures to temporarily block pain signals by targeting specific nerves, offering pain relief without the need for radiation or high doses of pain medication. This method can reduce the need for opioids and shorten hospital stays, making it a novel option for managing rib fracture pain. ^{1 2 3 4 6}

Research Team

Brian Ilfeld, MD

Principal Investigator

University of California, San Diego

Eligibility Criteria

Adults over 18 with moderate pain from 1-6 recent rib fractures, who are getting a single-injection nerve block. Excluded if on blood thinners, have infections at the probe site, need oxygen for lung issues, have certain cold-related diseases or diabetes, use opioids regularly, can't use an incentive spirometer, have other painful injuries needing opioids, or require continuous nerve blocks.

Inclusion Criteria

I am receiving a nerve block injection for my rib fracture pain.

I have 1-6 rib fractures from an injury within the last 60 hours, confirmed by imaging.

I experience moderate to severe pain (at least a 5 out of 10) in my fractured rib area even when resting.

Exclusion Criteria

Chest tube

Inability to contact the investigators during the treatment period, and vice versa (e.g., lack of telephone access)

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo cryoneurolysis or sham procedure for pain management following thoracic trauma

1 day

1 visit (in-person)

Post-treatment Monitoring

Participants are monitored for opioid consumption and pain levels over the first 2 months

8 weeks

Regular follow-ups (in-person and virtual)

Follow-up

Participants are monitored for long-term outcomes including chronic pain and pulmonary complications

12 months

Treatment Details

Interventions

• Cryoneurolysis
• Local anesthetic peripheral nerve block
• Sham Cryoneurolysis
• Sham peripheral nerve block

Trial Overview The trial is testing cryoneurolysis—a way to relieve pain by freezing nerves—against sham treatments in patients with traumatic rib fractures. It's a multicenter study where participants and researchers don't know who gets real treatment versus placebo to see if it effectively manages pain without opioids.

Participant Groups

Group I: Cryoneurolysis Active Control 2 Interventions

Active cryoneurolysis of the intercostal nerve of each fractured rib along with one cephalad and one caudad will be targeted: for each nerve the cryoneurolysis device will be triggered using 3 cycles of 2-minute nitrous oxide activation separated by 1-minute defrost periods (Epimed) or for the Varian: 5.5-minute \[all but 5 participants\] or 3-minute \[5th - 12th participants; changes based on new laboratory and subsequently clinical data\] argon activation (2000 psi starting at 100% power but decreased to keep return gas flow temperature warmer than -100C) followed by a 30-second helium defrost. For the active comparator, the gas will be deployed to the tip where a drop in temperature will result in cryoneurolysis.

Group II: Sham Procedure Placebo Group 2 Interventions

Sham cryoneurolysis of the intercostal nerve of each fractured rib along with one cephalad and one caudad will be targeted: for each nerve the cryoneurolysis device will be triggered using 3 cycles of 2-minute nitrous oxide activation separated by 1-minute defrost periods (Epimed) or for the Varian: 1 cycle of 5.5 minutes \[all but 5 participants\] or 3 minutes \[5th - 12th participants; changes based on new laboratory and subsequently clinical data\] of argon and 30 seconds of helium. However, for the sham comparator, the gas will NOT be deployed to the tip, there there will NOT be a drop in temperature, and NO cryoneurolysis will occur.

Cryoneurolysis is already approved in United States for the following indications:

Approved in United States as Cryoneurolysis for:

• Pain management for traumatic rib fractures
• Postoperative pain relief

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Congressionally Directed Medical Research Programs

Collaborator

Trials

59

Recruited

10,600+

Findings from Research

In a study of 241 patients undergoing surgical stabilization of rib fractures, those who received intercostal nerve cryoablation used significantly fewer opioids post-operatively and had shorter stays in the intensive care unit compared to those who did not receive cryoablation.

Cryoablation did not increase the time spent in surgery or the risk of pulmonary complications, making it a safe adjunctive treatment that enhances pain management without additional risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intercostal nerve cryoablation during surgical stabilization of rib fractures decreases post-operative opioid use, ventilation days, and intensive care days. Marturano, MN., Thakkar, V., Wang, H., et al.[2023]

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]

Intercostal nerve cryoablation (IC) during surgical stabilization of rib fractures (SSRF) was found to be safe and feasible, with no significant immediate or long-term complications reported among the 20 patients who underwent the procedure.

While the study did not show a significant reduction in pain scores or opioid use for the SSRF-IC group compared to the SSRF group, further research is needed to fully evaluate the analgesic efficacy of IC for rib fractures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intercostal nerve cryoablation during surgical stabilization of rib fractures. Choi, J., Min, JG., Jopling, JK., et al.[2023]

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]

Ultrasound-guided percutaneous cryoneurolysis of the intercostal nerves was successfully used to treat a 40-year-old male with severe post-thoracotomy pain syndrome (PTPS) that had persisted for two years.

The treatment resulted in a 75% reduction in pain immediately after the procedure, with sustained 50% pain relief for eight weeks, suggesting that this method is a safe and effective option for managing chronic PTPS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-Guided Percutaneous Cryoneurolysis for Post-Thoracotomy Pain Syndrome: A Case Report. Perese, J., Oswald, J., Gabriel, RA.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Intercostal nerve cryoablation during surgical stabilization of rib fractures decreases post-operative opioid use, ventilation days, and intensive care days. [2023]

2. 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]

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

Intercostal nerve cryoablation during surgical stabilization of rib fractures. [2023]

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

Ultrasound-Guided Percutaneous Cryoneurolysis for Post-Thoracotomy Pain Syndrome: A Case Report. [2023]