Ultrasound-Guided Percutaneous Cryoneurolysis to Treat Postoperative Pain After Mastectomy

NCT05444361 | Enrolling By Invitation DMC FDA Device

• 1 other identifier: CRYO for Mastectomy (DoD)
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 5

Brief Summary

Breast cancer is the most common type of cancer in women. Removal of the breast, called "mastectomy", is performed either when there is cancer-or an increased risk of cancer-in the breast. This can result in a lot of pain during the months after surgery. Opioids-"narcotics"-are the most common pain control method provided to patients; but they frequently do not relieve enough pain, have undesirable side effects like vomiting and constipation, and are sometimes misused which can lead to addiction. Mastectomy also frequently results in long-term pain which can interfere with physical and emotional functioning; and the more pain patients have immediately after surgery, the greater the risk of developing long-term pain. Numbing the nerves with local anesthetic can decrease the amount of short- and long-term pain experienced by patients, but even the longest types of these nerve blocks last for hours or days, and not the 1-2 months of pain typically following mastectomy. So, there is reason to believe that if the nerve blocks could be extended so that they last longer than the pain from surgery, short- and long-term pain might be avoided completely without the need for opioids. A prolonged nerve block may be provided by freezing the nerve using a technique called "cryoneurolysis". With cryoneurolysis and ultrasound machines, a small needle-like "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 become addictive. After 2-3 months, the nerve returns to normal functioning. The investigators have completed a small study suggesting that a single cryoneurolysis treatment may provide potent pain relief after mastectomy. The ultimate objectives of the proposed research study are to determine if temporarily freezing the nerves that go to the breast will decrease short-term pain, opioid use, physical and emotional dysfunction, and long-term pain following mastectomy when added to current and customary postoperative analgesics. 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 mastectomy.

Conditions

Mastectomy; Lymphedema

Outcome Measures

Primary Outcomes (2)

• Opioid consumption during first 2 postoperative months

  Cumulative opioid dose measured in oral oxycodone equivalents following recovery room discharge for 10 specific 24-hour time points over the first 2 months following surgery. With 10 time points (postoperative days 1, 2, 3, 4, 7, 14, 21, 30, 45 and 60), this will encompass 240 hours in total of the first 2 postoperative 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.

  Postoperative months 1 and 2, collected on days 1, 2, 3, 4, 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 postoperative months

  The area under the curve for the "average" daily pain scores over the first 2 postoperative months. At 10 specific time points the "average" pain score following recovery room discharge 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.

  Postoperative months 1 and 2, collected on days 1, 2, 3, 4, 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 (20)

• Opioid consumption

  Collected on postoperative days 1, 2, 3, 4, 7, 14, 21, 30, and 45; as well as months 2, 3, 6, 9, and 12

• Average Pain

  Collected on postoperative days 1, 2, 3, 4, 7, 14, 21, 30, and 45; as well as months 2, 3, 6, 9, and 12

• Worst/maximum Pain

  Collected on postoperative days 1, 2, 3, 4, 7, 14, 21, 30, and 45; as well as months 2, 3, 6, 9, and 12

• Least/lowest/minimal Pain

  Collected on postoperative days 3, 7, 14, 30, and 45; as well as months 2, 3, 6, 9, and 12

• Current Pain

  Collected on postoperative days 3, 7, 14, 30, and 45; as well as months 2, 3, 6, 9, and 12

Study Arms (2)

Cryoneurolysis

ACTIVE COMPARATOR

Cryoneurolysis of the 2nd-6th thoracic intercostal nerves will be treated on the ipsilateral surgical side (bilaterally for bilateral surgical procedures): for each nerve the cryoneurolysis device will be triggered using 1 cycle of 5.5-minute \[all but 4 participants: 064-067\] or 3 minutes \[only 4 participants 064-067; change based on new laboratory data, then changed back based on inadequate freeze\] argon activation (2000 psi and 100% power) followed by a 30-second helium defrost. For active probes, the gas will be deployed to the tip where a drop in temperature to approximately -70°C will result in cryoneurolysis.

Device: Cryoneurolysis

Sham Procedure

SHAM COMPARATOR

Sham cryoneurolysis of the 2nd-6th thoracic intercostal nerves will be applied on the ipsilateral surgical side (bilaterally for bilateral surgical procedures): for each nerve the cryoneurolysis device will be triggered using 2 cycles of 2-minute gas activation separated by 1-minute defrost periods (Epimed) or 1 cycle of 5.5 minutes \[all but 4 participants: 064-067\] or 3 minutes \[only 4 participants 064-067; change based on new laboratory data, then changed back based on inadequate freeze\] of argon and 30 seconds of helium (Varian). However, for sham probes, the gas is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.

Device: Sham Comparator

Interventions

Cryoneurolysis DEVICE

Cryoneurolysis of the 2nd-6th thoracic intercostal nerves will be treated on the ipsilateral surgical side (bilaterally for bilateral surgical procedures): for each nerve the cryoneurolysis device will be triggered using 2 cycles of 2-minute gas activation separated by 1-minute defrost periods (Epimed) or 1 cycle of 5.5 minutes \[all but 4 participants: 064-067\] or 3 minutes \[only 4 participants 064-067; change based on new laboratory data, then changed back based on inadequate freeze\] of argon and 30 seconds of helium (Varian). For active probes, the gas will be deployed to the tip where a drop in temperature to approximately -70°C will result in cryoneurolysis.

Also known as: Cryoablation

Cryoneurolysis

Sham Comparator DEVICE

Sham cryoneurolysis of the 2nd-6th thoracic intercostal nerves will be applied on the ipsilateral surgical side (bilaterally for bilateral surgical procedures): for each nerve the cryoneurolysis device will be triggered using 2 cycles of 2-minute gas activation separated by 1-minute defrost periods (Epimed) or 1 cycle of 5.5 minutes \[all but 4 participants: 064-067\] or 3 minutes \[only 4 participants 064-067; change based on new laboratory data, then changed back based on inadequate freeze\] of argon and 30 seconds of helium (Varian). However, for sham probes, the gas is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.

Also known as: Sham procedure

Sham Procedure

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
• Undergoing unilateral or bilateral total or modified radical mastectomy

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 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.
• 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.
• Neurologic deficit of the 2nd-6th ipsilateral intercostal nerves: cryoneurolysis is theoretically a potent analgesic, but it does not "heal" injured nerves. Therefore, pre-existing nerve deficits will confound the analgesia-related results.
• Chronic opioid use (daily use within the 2 weeks prior to surgery and duration of use \> 4 weeks, either by self-report or recorded previously in the medical record): individuals using opioids on a chronic basis will continue their baseline opioid requirements postoperatively. This will confound the analgesic results of the study.
• 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 injury65 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 err on the side of caution for study participants.
• Contralateral breast surgical procedure that does not include mastectomy.
• Inability to remain in contact with the investigators during the study period (e.g., lack of telephone access).

Sponsors & Collaborators

• University of California, San Diego: lead
• Department of Defense Congressionally Directed Medical Research Program: collaborator

Study Sites (5)

Cedars-Sinai

Los Angeles, California, 90048, United States

Location

University of California San Diego

San Diego, California, 92103, United States

Location

University of Florida

Gainesville, Florida, 32607, United States

Location

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Lymphedema

Interventions

Cryosurgery

Condition Hierarchy (Ancestors)

Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Ablation Techniques; Surgical Procedures, Operative

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, In Residence

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

Study Record Dates

• First Submitted: June 24, 2022
• First Posted: July 5, 2022
• Study Start: September 15, 2022
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): May 14, 2028
• Last Updated: October 21, 2025

Record last verified: 2025-10

Locations

US (5)