Ultrasound-Guided Percutaneous Cryoneurolysis to Treat Pain Following Thoracic Trauma

NCT06069154 | Enrolling By Invitation DMC FDA Device

• 1 other identifier: CRYO for Trauma (DoD)
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Rib Fracture; Rib Fracture Multiple

Outcome Measures

Primary Outcomes (2)

• Opioid consumption during first 2 post-intervention months

  Cumulative opioid dose measured in oral oxycodone equivalents following intervention for 9 specific 24-hour time points over the first 2 months following surgery. With 9 time points (post-intervention days 1, 2, 3, 7, 14, 21, 30, 45 and 60), this will encompass 216 hours in total of the first 2 post-intervention months. In order to claim that percutaneous cryoneurolysis is superior to usual and customary analgesia, at least one of Outcomes 1 and 2 must be superior while the other at least noninferior.

  Post-intervention months 1 and 2, collected on days 1, 2, 3, 7, 14, 21, 30, 45 and 60; at each collection time point, opioid use for the previous 24 hours will be recorded

• Average pain during first 2 post-intervention months

  The area under the curve for the "average" daily pain scores over the first 2 post-intervention months. At 9 specific time points the "average" pain score following the intervention will be measured using the numeric rating scale. This is a 0-10 Likert scale measuring pain level with 0=no pain and 10= worst imaginable pain. In order to claim that percutaneous cryoneurolysis is superior to usual and customary analgesia, at least one of Outcomes 1 and 2 must be superior while the other at least noninferior.

  Post-intervention months 1 and 2, collected on days 1, 2, 3, 7, 14, 21, 30, 45 and 60; at each collection time point, the "average" pain score for the previous 24 hours will be recorded

Secondary Outcomes (17)

• Opioid consumption

  Collected on post-intervention days 1, 2, 3, 7, 14, 21, 30, and 45; as well as months 2, 3, 6, 9, and 12

• Average pain

  Collected on post-intervention days 1, 2, 3, 7, 14, 21, 30, and 45; as well as months 2, 3, 6, 9, and 12

• Worst/maximum pain

  Collected on post-intervention days 1, 2, 3, 7, 14, 21, 30, and 45; as well as months 2, 3, 6, 9, and 12

• Least/lowest/minimal pain

  Collected on post-intervention days 1, 2, 3, 7, 14, 21, 30, and 45; as well as months 2, 3, 6, 9, and 12

• Current pain

  Collected on post-intervention days 1, 2, 3, 7, 14, 21, 30, and 45; as well as months 2, 3, 6, 9, and 12

Study Arms (2)

Cryoneurolysis

ACTIVE COMPARATOR

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.

Device: Cryoneurolysis; Procedure: Sham peripheral nerve block

Sham Procedure

SHAM COMPARATOR

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.

Procedure: Local anesthetic peripheral nerve block; Device: Sham Cryoneurolysis

Interventions

Cryoneurolysis DEVICE

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.

Also known as: cryoablation

Cryoneurolysis

Local anesthetic peripheral nerve block PROCEDURE

Due to the pragmatic design of this trial, study participation will not alter an institution's current practice. Examples of peripheral nerve blocks include paravertebral, erector spinae plane, and serratus anterior nerve blocks. The injectate through the introducer will depend on the treatment group: for participants of the control group, ropivacaine 0.5% or bupivacaine 0.375% (both with epinephrine 1:400,000) will be injected (volume determined by institutional standard-of-care). This will provide a peripheral nerve block for the control group.

Sham Procedure

Sham Cryoneurolysis DEVICE

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 will NOT be a drop in temperature, and NO cryoneurolysis will occur.

Also known as: sham cryoablation

Sham Procedure

Sham peripheral nerve block PROCEDURE

Due to the pragmatic design of this trial, study participation will not alter an institution's current practice. Examples of peripheral nerve blocks include paravertebral, erector spinae plane, and serratus anterior nerve blocks: for participants allocated to the cryoneurolysis group (experimental group), normal saline will be injected for the peripheral nerve block. This will result in a sham/placebo nerve block for the experimental group.

Cryoneurolysis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients of at least 18 years of age
• A total of 1-6 traumatic rib fractures confirmed by imaging at least 3 cm distal to the costotransverse joint sustained within the previous 60 h (bilateral fractures are acceptable, but the total of the two sides combined must not exceed 6 fractures)
• Pain in the fractured rib(s) region rated at least moderate (5 on the 0-10 Numeric Rating Scale) at rest
• Undergoing a single-injection peripheral nerve block to treat the pain of the rib fracture(s)

You may not qualify if:

• Anticoagulation or bleeding disorder: introduction of the percutaneous cryoneurolysis probe has a risk of hemorrhage similar to the percutaneous insertion of a similar gauge needle; but an anticoagulated state will increase the risk of hemorrhage (aspirin in doses for cardiothoracic/stroke prophylaxis \[≤ 325 mg\] are acceptable).
• Infection at the site of probe introduction: percutaneous insertion of the probe through a cutaneous infection would bring an unacceptable risk of introducing the infection to deeper tissues.
• Pulmonary disease or injury requiring supplemental oxygen: one theoretical risk of cryoneurolysis is a unilateral pneumothorax (not reported) which could result in a compromised pulmonary state for patients who require supplemental oxygen at baseline.
• Neurologic deficit of the intercostal nerves of the fractured ribs: cryoneurolysis is theoretically a potent analgesic, but it does not "heal" injured nerves. Therefore, nerve deficits-either pre-existing or due to the trauma-will confound the analgesia-related results.
• Possessing any contraindication to decreased temperature such as cryoglobulinemia, cryofibrinogenemia, cold urticaria paroxysmal cold hemoglobinuria, or Raynaud's disease: the decreased temperature accompanying cryoneurolysis could result in local tissue/vascular compromise for patients with any of these cold-triggered syndromes/diseases.
• Insulin-dependent diabetes: laboratory studies have demonstrated impaired nerve regeneration in diabetic animals, and diabetes in patients can lead to impaired regeneration of axons and recovery following investigational nerve injury as well as focal neuropathies such as ulnar neuropathy and carpal tunnel syndrome. Whether these findings are applicable to cryoneurolysis in patients with diabetes remains unknown, but we prefer to error on the side of caution for study participants.
• Chronic opioid use (daily use within the 2 weeks prior to the fracture and duration of use \> 4 weeks): individuals using opioids on a chronic basis will continue their baseline opioid requirements following the traumatic event. This will confound the analgesic results of the study.
• Inability to use an incentive spirometer: One of the Specific Aims involves improving functioning by decreasing pain using cryoneurolysis, and this will be evaluated using an incentive spirometer. For this reason, patients who are intubated or for whom there is anticipation of intubation will be excluded.
• Any injury outside of the fractured rib(s) which results in moderate pain (NRS \> 3) and/or anticipated to require opioid analgesics: such injuries would confound the results for the intervention under investigation.
• An existing or planned continuous neuraxial or peripheral nerve block.
• Fracture of the 1st rib on either side
• Flail chest (3 or more adjacent ribs, each fractured in more than one location to create a free-floating segment)
• Chest tube
• Any degree of decreased mental capacity as determined by the surgical service or investigators.
• Inability to contact the investigators during the treatment period, and vice versa (e.g., lack of telephone access).

Sponsors & Collaborators

• University of California, San Diego: lead
• Congressionally Directed Medical Research Programs: collaborator

Study Sites (5)

University of California, San Diego

La Jolla, California, 92037, United States

Location

Walter Reed National Military Medical Center

Bethesda, Maryland, 20814, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Texas, Houston

Houston, Texas, 77054, United States

Location

Related Publications (2)

• Finneran Iv JJ, Gabriel RA, Swisher MW, Berndtson AE, Godat LN, Costantini TW, Ilfeld BM. Ultrasound-guided percutaneous intercostal nerve cryoneurolysis for analgesia following traumatic rib fracture -a case series. Korean J Anesthesiol. 2020 Oct;73(5):455-459. doi: 10.4097/kja.19395. Epub 2019 Nov 5.

  PMID: 31684715 BACKGROUND

• Ilfeld BM, Finneran JJ. Cryoneurolysis and Percutaneous Peripheral Nerve Stimulation to Treat Acute Pain. Anesthesiology. 2020 Nov 1;133(5):1127-1149. doi: 10.1097/ALN.0000000000003532.

  PMID: 32898231 BACKGROUND

MeSH Terms

Conditions

Rib Fractures

Interventions

Cryosurgery

Condition Hierarchy (Ancestors)

Fractures, Bone; Wounds and Injuries; Thoracic Injuries

Intervention Hierarchy (Ancestors)

Ablation Techniques; Surgical Procedures, Operative

Study Officials

• Brian Ilfeld, MD, MS

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All investigators, participants, and clinical staff will be masked to treatment group assignment, with the only exception being the unmasked individual who performs the procedure (and will not have subsequent contact with the participant).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Anesthesiology

Model Details: Pragmatic, multicenter, randomized, triple-masked, sham-controlled clinical trial

Study Record Dates

• First Submitted: October 1, 2023
• First Posted: October 5, 2023
• Study Start: October 30, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 20, 2025

Record last verified: 2025-10

Locations

US (5)