Cryoanalgesia to Prevent Acute and Chronic Pain Following Surgery: A Randomized, Double-Masked, Sham-Controlled Study

• ClinicalTrials.gov Identifier: NCT03578237
• Recruitment Status: Completed
• First Posted: July 6, 2018
• Results First Posted: February 10, 2023
• Last Update Posted: February 10, 2023
• Sponsor: University of California, San Diego
• Collaborators: Epimed International; Myoscience (prior to merger with Pacira Pharmaceuticals)
• Information provided by (Responsible Party): Brian M. Ilfeld, MD, MS, University of California, San Diego

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Outcomes Assessor); Primary Purpose: Prevention
• Conditions: Mastectomy; Upper Limb Amputation Below Elbow; Upper Limb Amputation Above Elbow; Lower Limb Amputation Below Knee; Lower Limb Amputation Above Knee; Knee Arthropathy; Shoulder Arthroplasty; Rotator Cuff Repair; Video-Assisted Thoracoscopic Surgery (VATS); Skin Grafting
• Interventions: Device: Cryoneurolysis (active); Device: Sham cryoneurolysis procedure
• Enrollment: 99

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
Arm/Group Description	Receiving active cryoneurolysis Cryoneurolysis (active): Mastectomy (subjects 1-18): Myoscience Iovera device: full cryo cycle. Mastectomy (subjects 19-end) and all other procedures: Epimed PainBlocker device: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with an active probe which results in a decrease in temperature	Receiving sham cryoneurolysis procedure Sham cryoneurolysis procedure: Mastectomy (subjects 1-18): Myoscience Iovera device: simulated full cryo cycle without administering gas to the probe. Mastectomy (subjects 19-end) and all other procedures: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with a SHAM probe that does not deliver gas to the tip or result in a drop in temperature
Period Title: Postoperative Days 0-21
Started	51	48
Completed	51	48
Not Completed	0	0
Period Title: Postoperative Day 0 - Month 12
Started	51	48
Completed	37	32
Not Completed	14	16
Reason Not Completed
Timepoints past 21 days were only for amputee and mastectomy subjects and not others	14	16

Baseline Characteristics

Arm/Group Title		Treatment (Active Cryoneurolysis)	Sham	Total
Arm/Group Description		Receiving active cryoneurolysis Cryoneurolysis (active): Mastectomy (subjects 1-18): Myoscience Iovera device: full cryo cycle. Mastectomy (subjects 19-end) and all other procedures: Epimed PainBlocker device: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with an active probe which results in a decrease in temperature	Receiving sham cryoneurolysis procedure Sham cryoneurolysis procedure: Mastectomy (subjects 1-18): Myoscience Iovera device: simulated full cryo cycle without administering gas to the probe. Mastectomy (subjects 19-end) and all other procedures: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with a SHAM probe that does not deliver gas to the tip or result in a drop in temperature	Total of all reporting groups
Overall Number of Baseline Participants		51	48	99
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	51 participants	48 participants	99 participants
		51.1 (15)	52 (16)	51.5 (15.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	51 participants	48 participants	99 participants
	Female	40 78.4%	31 64.6%	71 71.7%
	Male	11 21.6%	17 35.4%	28 28.3%
Race and Ethnicity Not Collected [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	0 participants	0 participants	0 participants
				0
		[1] Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Weight; Mean (Standard Deviation); Unit of measure: Kilograms
	Number Analyzed	51 participants	48 participants	99 participants
		70.6 (13.7)	68.8 (14.8)	69.6 (14.2)
Height; Mean (Standard Deviation); Unit of measure: Centimeters
	Number Analyzed	51 participants	48 participants	99 participants
		165.1 (8.0)	165.7 (7.6)	165.4 (7.7)
Body Mass Index; Mean (Standard Deviation); Unit of measure: Kg/m^2
	Number Analyzed	51 participants	48 participants	99 participants
		25.9 (4.6)	25.0 (4.5)	25.4 (4.6)

Outcome Measures

1. Primary Outcome

Title	Average Pain (Mastectomy Subjects Only)
Description	Measured with the 0-10 numeric rating scale as part of the Brief Pain Inventory, with 0 equivalent to no pain and 10 equivalent to the worst imaginable pain
Time Frame	afternoon of postoperative day 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
Arm/Group Description:	Receiving active cryoneurolysis Cryoneurolysis (active): Mastectomy (subjects 1-18): Myoscience Iovera device: full cryo cycle. Mastectomy (subjects 19-end) and all other procedures: Epimed PainBlocker device: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with an active probe which results in a decrease in temperature	Receiving sham cryoneurolysis procedure Sham cryoneurolysis procedure: Mastectomy (subjects 1-18): Myoscience Iovera device: simulated full cryo cycle without administering gas to the probe. Mastectomy (subjects 19-end) and all other procedures: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with a SHAM probe that does not deliver gas to the tip or result in a drop in temperature
Overall Number of Participants Analyzed	51	48
Median (Inter-Quartile Range); Unit of Measure: score on a scale
	0.0; (0 to 1.4)	3.0; (2.0 to 5.0)

2. Secondary Outcome

Title	Analgesic Consumption
Description	Analgesic consumption for previous 24 hours
Time Frame	Postoperative days 1, 2, 3, 4, 7, 14, 21, as well as months 1, 3, 6, and 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
Arm/Group Description:	Receiving active cryoneurolysis Cryoneurolysis (active): Mastectomy (subjects 1-18): Myoscience Iovera device: full cryo cycle. Mastectomy (subjects 19-end) and all other procedures: Epimed PainBlocker device: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with an active probe which results in a decrease in temperature	Receiving sham cryoneurolysis procedure Sham cryoneurolysis procedure: Mastectomy (subjects 1-18): Myoscience Iovera device: simulated full cryo cycle without administering gas to the probe. Mastectomy (subjects 19-end) and all other procedures: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with a SHAM probe that does not deliver gas to the tip or result in a drop in temperature
Overall Number of Participants Analyzed	51	48
Mean (Standard Deviation); Unit of Measure: tablets of oxycodone (5 mg tablets)
Postoperative Day 1	1.2 (2.3)	3.3 (4.5)
Postoperative Day 2	1.0 (1.6)	4.1 (3.8)
Postoperative Day 3	.8 (1.9)	3.2 (3.7)
Postoperative Day 4	0.7 (1.5)	2.7 (3.5)
Postoperative Day 7	0.5 (1.2)	1.5 (2.2)
Postoperative Day 14	0.2 (0.6)	0.5 (1.3)
Postoperative Day 21	0.1 (0.5)	0.3 (0.8)
Postoperative Month 1	0 (0)	0 (0)
Postoperative Month 3	0 (0)	0 (0)
Postoperative Month 6	0 (0)	0 (0)
Postoperative Month 12	0 (0)	0 (0)

3. Secondary Outcome

Title	Brief Pain Inventory (Interference Subscale)
Description	The Brief Pain Inventory short form (interference scale) is designed to assess pain's impact on physical and emotional functioning. It has established reliability and validity, with minimal inter-rater discordance, and is recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus statement. The interference domaine is comprised of 7 questions involving the degree of pain's interference on physical and emotional functioning using a 0-10 Likert scale (0 = none; 10 = complete). The scale is thus 0-70 with higher scores equivalent to more interference due to pain>
Time Frame	Months 1, 3, 6, and 12

Outcome Measure Data

Analysis Population Description

mastectomy and amputee participants only (other participants did not have outcome measures collected for these time points)

Arm/Group Title	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
Arm/Group Description:	Receiving active cryoneurolysis Cryoneurolysis (active): Mastectomy (subjects 1-18): Myoscience Iovera device: full cryo cycle. Mastectomy (subjects 19-end) and all other procedures: Epimed PainBlocker device: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with an active probe which results in a decrease in temperature	Receiving sham cryoneurolysis procedure Sham cryoneurolysis procedure: Mastectomy (subjects 1-18): Myoscience Iovera device: simulated full cryo cycle without administering gas to the probe. Mastectomy (subjects 19-end) and all other procedures: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with a SHAM probe that does not deliver gas to the tip or result in a drop in temperature
Overall Number of Participants Analyzed	37	32
Mean (Standard Deviation); Unit of Measure: units on a scale
Month 1	0 (0)	4.1 (9.2)
Month 3	0 (0)	0.6 (2.9)
Month 6	0 (0)	1.1 (2.3)
Month 12	0 (0)	0.3 (0.9)

4. Secondary Outcome

Title	Worst Pain Measured on the 11 Point Numeric Rating Scale
Description	The subjects' perception of their worst level pain in the previous 24 hours measured with the 0-10 numeric rating scale as part of the Brief Pain Inventory, with 0 equivalent to no pain and 10 equivalent to the worst imaginable pain
Time Frame	Postoperative days 1, 2, 3, 4, 7, 14, and 21

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
Arm/Group Description:	Receiving active cryoneurolysis Cryoneurolysis (active): Mastectomy (subjects 1-18): Myoscience Iovera device: full cryo cycle. Mastectomy (subjects 19-end) and all other procedures: Epimed PainBlocker device: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with an active probe which results in a decrease in temperature	Receiving sham cryoneurolysis procedure Sham cryoneurolysis procedure: Mastectomy (subjects 1-18): Myoscience Iovera device: simulated full cryo cycle without administering gas to the probe. Mastectomy (subjects 19-end) and all other procedures: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with a SHAM probe that does not deliver gas to the tip or result in a drop in temperature
Overall Number of Participants Analyzed	51	48
Mean (Standard Deviation); Unit of Measure: score on a scale
Postoperative Day 1	3.7 (2.5)	5.5 (2.4)
Postoperative Day 2	3.3 (2.9)	5.6 (2.7)
Postoperative Day 3	2.8 (2.7)	5.1 (2.8)
Postoperative Day 4	2.4 (2.6)	4.3 (2.7)
Postoperative Day 7	2.4 (2.4)	3.7 (2.4)
Postoperative Day 14	1.6 (2.4)	3.1 (2.3)
Postoperative Day 21	1.4 (2.6)	3.0 (2.5)

5. Secondary Outcome

Title	Average Pain Measured on the 11 Point Numeric Rating Scale
Description	The subjects' perception of their average level pain in the previous 24 hours measured with the 0-10 numeric rating scale as part of the Brief Pain Inventory, with 0 equivalent to no pain and 10 equivalent to the worst imaginable pain
Time Frame	Postoperative days 1, 2, 3, 4, 7, 14, and 21

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
Arm/Group Description:	Receiving active cryoneurolysis Cryoneurolysis (active): Mastectomy (subjects 1-18): Myoscience Iovera device: full cryo cycle. Mastectomy (subjects 19-end) and all other procedures: Epimed PainBlocker device: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with an active probe which results in a decrease in temperature	Receiving sham cryoneurolysis procedure Sham cryoneurolysis procedure: Mastectomy (subjects 1-18): Myoscience Iovera device: simulated full cryo cycle without administering gas to the probe. Mastectomy (subjects 19-end) and all other procedures: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with a SHAM probe that does not deliver gas to the tip or result in a drop in temperature
Overall Number of Participants Analyzed	51	48
Mean (Standard Deviation); Unit of Measure: score on a scale
Postoperative day 1	1.5 (1.8)	3.2 (2.1)
Postoperative day 2	1.5 (2.0)	3.3 (1.9)
Postoperative day 3	1.2 (2.1)	2.8 (1.9)
Postoperative day 4	1.2 (2)	2.4 (1.9)
Postoperative day 7	0.8 (1.3)	2 (1.9)
Postoperative day 14	0.9 (1.9)	1.6 (1.5)
Postoperative day 21	.7 (1.5)	1.6 (1.8)

6. Secondary Outcome

Title	Difficultly Sleeping Due to Pain
Description	Difficulty sleeping due to pain (binary answer: yes or no; not based on a scale or instrument). The numbers presented in the results are the number of participants in each treatment group answering YES, they DID have difficulty sleeping due to pain
Time Frame	Postoperative days 1, 2, 3, 4, 7, 14, and 21

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
Arm/Group Description:	Receiving active cryoneurolysis Cryoneurolysis (active): Mastectomy (subjects 1-18): Myoscience Iovera device: full cryo cycle. Mastectomy (subjects 19-end) and all other procedures: Epimed PainBlocker device: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with an active probe which results in a decrease in temperature	Receiving sham cryoneurolysis procedure Sham cryoneurolysis procedure: Mastectomy (subjects 1-18): Myoscience Iovera device: simulated full cryo cycle without administering gas to the probe. Mastectomy (subjects 19-end) and all other procedures: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with a SHAM probe that does not deliver gas to the tip or result in a drop in temperature
Overall Number of Participants Analyzed	51	48
Measure Type: Count of Participants; Unit of Measure: Participants
Postoperative day 1	5 9.8%	11 22.9%
Postoperative day 2	6 11.8%	11 22.9%
Postoperative day 3	6 11.8%	13 27.1%
Postoperative day 4	3 5.9%	10 20.8%
Postoperative day 7	4 7.8%	11 22.9%
Postoperative day 14	4 7.8%	7 14.6%
Postoperative day 21	4 7.8%	7 14.6%

7. Secondary Outcome

Title	Number of Awakenings
Description	Number of awakenings from sleep due to pain (simply the number of times of awakenings--not based on a scale or instrument)
Time Frame	Postoperative days 1, 2, 3, 4, 7, 14, and 21

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
Arm/Group Description:	Receiving active cryoneurolysis Cryoneurolysis (active): Mastectomy (subjects 1-18): Myoscience Iovera device: full cryo cycle. Mastectomy (subjects 19-end) and all other procedures: Epimed PainBlocker device: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with an active probe which results in a decrease in temperature	Receiving sham cryoneurolysis procedure Sham cryoneurolysis procedure: Mastectomy (subjects 1-18): Myoscience Iovera device: simulated full cryo cycle without administering gas to the probe. Mastectomy (subjects 19-end) and all other procedures: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with a SHAM probe that does not deliver gas to the tip or result in a drop in temperature
Overall Number of Participants Analyzed	51	48
Mean (Standard Deviation); Unit of Measure: Awakenings
Postoperative day 1	0.1 (0.6)	.8 (1.4)
Postoperative day 2	.3 (1)	.5 (1)
Postoperative day 3	.4 (1.2)	.9 (1.6)
Postoperative day 4	.3 (.9)	.5 (.8)
Postoperative day 7	.1 (.4)	.5 (1)
Postoperative day 14	.3 (1)	.3 (.6)
Postoperative day 21	.2 (.9)	.4 (.9)

8. Secondary Outcome

Title	Nausea
Description	Nausea measured on a 0-10 scale with 0=no nausea and 10=vomiting; thus higher on the scale is worse
Time Frame	Postoperative days 1, 2, 3, 4, 7, 14, and 21

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
Arm/Group Description:	Receiving active cryoneurolysis Cryoneurolysis (active): Mastectomy (subjects 1-18): Myoscience Iovera device: full cryo cycle. Mastectomy (subjects 19-end) and all other procedures: Epimed PainBlocker device: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with an active probe which results in a decrease in temperature	Receiving sham cryoneurolysis procedure Sham cryoneurolysis procedure: Mastectomy (subjects 1-18): Myoscience Iovera device: simulated full cryo cycle without administering gas to the probe. Mastectomy (subjects 19-end) and all other procedures: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with a SHAM probe that does not deliver gas to the tip or result in a drop in temperature
Overall Number of Participants Analyzed	51	48
Mean (Standard Deviation); Unit of Measure: units on a scale
Postoperative day 1	.5 (1.5)	.6 (2.1)
Postoperative day 2	.1 (.5)	.3 (.9)
Postoperative day 3	0 (0)	0.3 (1.1)
Postoperative day 4	.2 (1.1)	.1 (.9)
Postoperative day 7	.1 (.3)	.3 (1.7)
Postoperative day 14	0 (0)	0 (0)
Postoperative day 21	0 (0)	0 (0)

9. Secondary Outcome

Title	Phantom Pain Occurences [Mastectomy & Amputation]
Description	How many times in the previous 3 days subject experienced phantom pain (the number of times experienced--not based on a scale or instrument)
Time Frame	Postoperative months 1, 3, 6, and 12

Outcome Measure Data

Analysis Population Description

mastectomy and amputee participants only (other participants did not have outcome measures collected for these time points)

Arm/Group Title	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
Arm/Group Description:	Receiving active cryoneurolysis Cryoneurolysis (active): Mastectomy (subjects 1-18): Myoscience Iovera device: full cryo cycle. Mastectomy (subjects 19-end) and all other procedures: Epimed PainBlocker device: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with an active probe which results in a decrease in temperature	Receiving sham cryoneurolysis procedure Sham cryoneurolysis procedure: Mastectomy (subjects 1-18): Myoscience Iovera device: simulated full cryo cycle without administering gas to the probe. Mastectomy (subjects 19-end) and all other procedures: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with a SHAM probe that does not deliver gas to the tip or result in a drop in temperature
Overall Number of Participants Analyzed	37	32
Mean (Standard Deviation); Unit of Measure: Occurrences
Month 1	0 (0)	0.5 (1.8)
Month 3	0 (0)	9.8 (2.5)
Month 6	0 (0)	4.0 (1.9)
Month 12	0 (0)	0.4 (1.2)

10. Secondary Outcome

Title	Phantom Pain Duration [Mastectomy & Amputation]
Description	The average duration of phantom pain occurrences in the previous 3 days
Time Frame	Postoperative months 1, 3, 6, and 12

Outcome Measure Data

Analysis Population Description

mastectomy and amputee participants only (other participants did not have outcome measures collected for these time points)

Arm/Group Title	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
Arm/Group Description:	Receiving active cryoneurolysis Cryoneurolysis (active): Mastectomy (subjects 1-18): Myoscience Iovera device: full cryo cycle. Mastectomy (subjects 19-end) and all other procedures: Epimed PainBlocker device: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with an active probe which results in a decrease in temperature	Receiving sham cryoneurolysis procedure Sham cryoneurolysis procedure: Mastectomy (subjects 1-18): Myoscience Iovera device: simulated full cryo cycle without administering gas to the probe. Mastectomy (subjects 19-end) and all other procedures: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with a SHAM probe that does not deliver gas to the tip or result in a drop in temperature
Overall Number of Participants Analyzed	37	32
Mean (Standard Deviation); Unit of Measure: hours
Month 1	0 (0)	0.1 (0.2)
Month 3	0 (0)	0 (0.2)
Month 6	0 (0)	5.1 (20.1)
Month 12	0 (0)	0 (0.2)

11. Secondary Outcome

Title	Phantom Sensation Occurrences [Mastectomy & Amputation]
Description	How many times in the previous 3 days subject experienced phantom sensations (the number of times experienced--not based on a scale or instrument). This outcome differs from "phantom pain occurrences" in that for this outcome no pain is necessary; rather, participants feel the missing body part is actually there, when it is not--yet it is not a painful sensation.
Time Frame	Postoperative months 1, 3, 6, and 12

Outcome Measure Data

Analysis Population Description

mastectomy and amputee participants only (other participants did not have outcome measures collected for these time points)

Arm/Group Title	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
Arm/Group Description:	Receiving active cryoneurolysis Cryoneurolysis (active): Mastectomy (subjects 1-18): Myoscience Iovera device: full cryo cycle. Mastectomy (subjects 19-end) and all other procedures: Epimed PainBlocker device: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with an active probe which results in a decrease in temperature	Receiving sham cryoneurolysis procedure Sham cryoneurolysis procedure: Mastectomy (subjects 1-18): Myoscience Iovera device: simulated full cryo cycle without administering gas to the probe. Mastectomy (subjects 19-end) and all other procedures: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with a SHAM probe that does not deliver gas to the tip or result in a drop in temperature
Overall Number of Participants Analyzed	37	32
Mean (Standard Deviation); Unit of Measure: incidences
Month 1	0 (0)	0 (0)
Month 3	0 (0)	1.2 (3.1)
Month 6	0 (0)	0.5 (1.7)
Month 12	0 (0)	10.3 (26.7)

12. Secondary Outcome

Title	Phantom Sensation Duration [Mastectomy & Amputation]
Description	The average duration of phantom sensation occurrences in the previous 3 days. This outcome differs from "phantom pain duration" in that for this outcome no pain is necessary; rather, participants feel the missing body part is actually there, when it is not--yet it is not a painful sensation.
Time Frame	Postoperative months 1, 3, 6, and 12

Outcome Measure Data

Analysis Population Description

mastectomy and amputee participants only (other participants did not have outcome measures collected for these time points)

Arm/Group Title	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
Arm/Group Description:	Receiving active cryoneurolysis Cryoneurolysis (active): Mastectomy (subjects 1-18): Myoscience Iovera device: full cryo cycle. Mastectomy (subjects 19-end) and all other procedures: Epimed PainBlocker device: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with an active probe which results in a decrease in temperature	Receiving sham cryoneurolysis procedure Sham cryoneurolysis procedure: Mastectomy (subjects 1-18): Myoscience Iovera device: simulated full cryo cycle without administering gas to the probe. Mastectomy (subjects 19-end) and all other procedures: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with a SHAM probe that does not deliver gas to the tip or result in a drop in temperature
Overall Number of Participants Analyzed	37	32
Mean (Standard Deviation); Unit of Measure: hours
Month 1	0 (0)	0 (0)
Month 3	0 (0)	0.1 (0.3)
Month 6	0 (0)	1.7 (8.9)
Month 12	0 (0)	7.8 (26.8)

13. Secondary Outcome

Title	Residual Limb or Wound Pain Occurences
Description	How many times in the previous 3 days subject experienced residual limb or wound pain (the number of times experienced--not based on a scale or instrument)
Time Frame	Postoperative months 1, 3, 6, and 12

Outcome Measure Data

Analysis Population Description

mastectomy and amputee participants only (other participants did not have outcome measures collected for these time points)

Arm/Group Title	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
Arm/Group Description:	Receiving active cryoneurolysis Cryoneurolysis (active): Mastectomy (subjects 1-18): Myoscience Iovera device: full cryo cycle. Mastectomy (subjects 19-end) and all other procedures: Epimed PainBlocker device: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with an active probe which results in a decrease in temperature	Receiving sham cryoneurolysis procedure Sham cryoneurolysis procedure: Mastectomy (subjects 1-18): Myoscience Iovera device: simulated full cryo cycle without administering gas to the probe. Mastectomy (subjects 19-end) and all other procedures: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with a SHAM probe that does not deliver gas to the tip or result in a drop in temperature
Overall Number of Participants Analyzed	37	32
Mean (Standard Deviation); Unit of Measure: Occurrences
Month 1	0.9 (1.6)	20 (37.1)
Month 3	0 (0)	4.4 (18.4)
Month 6	0.1 (0.4)	5.3 (18.4)
Month 12	0.1 (0.4)	1.1 (3.4)

14. Secondary Outcome

Title	Residual Limb or Wound Pain Duration
Description	The average duration of residual limb or wound pain occurrences in the previous 3 days
Time Frame	Postoperative months 1, 3, 6, and 12

Outcome Measure Data

Analysis Population Description

mastectomy and amputee participants only (other participants did not have outcome measures collected for these time points)

Arm/Group Title	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
Arm/Group Description:	Receiving active cryoneurolysis Cryoneurolysis (active): Mastectomy (subjects 1-18): Myoscience Iovera device: full cryo cycle. Mastectomy (subjects 19-end) and all other procedures: Epimed PainBlocker device: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with an active probe which results in a decrease in temperature	Receiving sham cryoneurolysis procedure Sham cryoneurolysis procedure: Mastectomy (subjects 1-18): Myoscience Iovera device: simulated full cryo cycle without administering gas to the probe. Mastectomy (subjects 19-end) and all other procedures: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with a SHAM probe that does not deliver gas to the tip or result in a drop in temperature
Overall Number of Participants Analyzed	37	32
Mean (Standard Deviation); Unit of Measure: hours
Month 1	0.1 (0.3)	17.6 (37.8)
Month 3	0 (0)	3.5 (18.4)
Month 6	0 (0.2)	5.3 (20.1)
Month 12	0 (0)	0 (0.2)

Adverse Events

Time Frame	Mastectomy participants: 1 year Amputation participants: 1 year Burn participants: 21 days Total knee arthroplasty participants: 21 days
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
Arm/Group Description	Receiving active cryoneurolysis Cryoneurolysis (active): Mastectomy (subjects 1-18): Myoscience Iovera device: full cryo cycle. Mastectomy (subjects 19-end) and all other procedures: Epimed PainBlocker device: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with an active probe which results in a decrease in temperature	Receiving sham cryoneurolysis procedure Sham cryoneurolysis procedure: Mastectomy (subjects 1-18): Myoscience Iovera device: simulated full cryo cycle without administering gas to the probe. Mastectomy (subjects 19-end) and all other procedures: 3 cycles of 2-minute gas activation separated by 1-minute defrost periods with a SHAM probe that does not deliver gas to the tip or result in a drop in temperature
All-Cause Mortality
	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/51 (0.00%)	2/48 (4.17%)
Serious Adverse Events
	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/51 (0.00%)	0/48 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	ACTIVE Cryoneurolysis	SHAM Cryoneurolysis
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/51 (0.00%)	0/48 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Program Manager
• Organization: University of California San Diego
• Phone: (858) 220-5714
• EMail: baabdullah@health.ucsd.edu

• Responsible Party: Brian M. Ilfeld, MD, MS, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT03578237
• Other Study ID Numbers: Cryo Prevention PILOTs
• First Submitted: June 25, 2018
• First Posted: July 6, 2018
• Results First Submitted: December 5, 2022
• Results First Posted: February 10, 2023
• Last Update Posted: February 10, 2023