The cryoICE™ CryoAnalgesia Study For Pain Management in Post thoRacic Procedures Via intercOSTal Cryoanalgesia (FROST) (FROST)

The investigators propose to assess whether intra-operative intercostal cryoanalgesia using the cryoICE® probe (AtriCure®, Inc., 7555 Innovation Way, Mason, Ohio) provides superior post-operative analgesic efficacy as compared to current pain management in patients undergoing unilateral thoracotomy cardiac procedures.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Device: Cryoanalgesia; Drug: Standard of Care

Detailed Description

Completion of the proposed study will for the first time demonstrate efficacy of intercostal cryoanalgesia in patients undergoing minimally invasive cardiac procedures. Furthermore, results of this study may have a pivotal role in supporting future clinical outcome trials for intercostal cryoanalgesia therapy.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California (USC)
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • United Heart and Vascular Institute - Allina
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 - 85 years male or female
• Patients undergoing unilateral thoracotomy cardiac procedures (with the exception of Aortic Aneurysm repair as sole treatment)
• Acceptable surgical candidate, including use of general anesthesia
• Willing and able to provide written informed consent
• Willing and able to return for scheduled follow-up visits

Exclusion Criteria:

• Cardiac valve surgical procedure via conventional full sternotomy
• Procedures that require a posterolateral thoracotomy
• Current pregnancy
• Current use of prescription opioids
• FEV1 < 40% predicted
• Documented myocardial infarction within 30 days of signing Informed Consent Form (ICF)
• Documented psychiatric disease
• Documented chronic pain syndrome
• Documented history of substance abuse
• Patient currently enrolled in another research study that could directly affect results of either study
• Physical or mental condition that would interfere with patient's self-assessment of pain
• Disqualifying medical condition per investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cryoanalgesia + Standard of Care (SOC); Cryoanalgesia in Conjunction with Standard of Care. Up to 5 sessions of cryoanalgesia for 120 seconds per session.	Device: Cryoanalgesia; AtriCure® cryoICE cryo-ablation system; Other Names: cryoICE; Drug: Standard of Care; Institutional SOC for pain management will be followed.; Other Names: SOC
Active Comparator: Standard of Care; Institutional SOC for pain management will be followed. The use of local post-operative pain management techniques (i.e., intercostal, peri-vertebral, or any other acceptable method) is permitted for both treatment groups up to 24 hours post-operatively according to institutional standard of care.	Drug: Standard of Care; Institutional SOC for pain management will be followed.; Other Names: SOC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Outcome 1: Forced Expiratory Volume (FEV1) at 48-Hours Post-Surgery	Forced Expiratory Volume (FEV1) is the measurement of how much air, in volume, that a person can exhale with a forced breath. It is measured using a spirometer device.	48-hours post-surgery
Primary Outcome 2: Visual Analogue Scale (VAS) Pain in the Surgical Region at 48-Hours Post-Surgery	The Visual Analogue Scale (VAS) uses a picture of a linear scale that shows numbers 0-10 with 0 being the least amount of pain and 10 being the most amount of pain. This outcome looked at pain in the surgical region specifically.	48-hours post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Outcome 1: Spirometry Assessments at 48-Hours Post-Extubation	Spirometry assessments measured included: forced expiratory volume (FEV1), forced vital capacity (FVC) and slow vital capacity (SVC), all of which are measured with a spirometer. FEV1 is the amount of air forcibly expired during the first second of breath, FVC is the total volume of air expired over the whole forced breath and SVC is the total volume over the whole breath but at a slow pace, not forced.	48-hours post-extubation
Secondary Outcome 2: Visual Analogue Scale (VAS) Pain at the 72, 96 and 120-Hours Post-Op Time Points	The Visual Analogue Scale (VAS) uses a picture of a linear scale that shows numbers 0-10 with 0 being the least amount of pain and 10 being the most amount of pain. This outcome looked at pain in the surgical region specifically.	72-, 96- and 120-hours Post-Op
Secondary Outcome 3: Allodynia at the 3 and 6 Month Visit	Allodynia is pain around surgical site. It is pain that occurs from stimuli that are not normally painful such as a light touch or a brush of hair around where the surgery took place.	3 and 6 Months
Secondary Outcome 4: Duration of Oral Endotracheal Intubation From Extubation Until the Patient Leaves the Operating Room	Oral endotracheal intubation is where a patient has a tube placed down their throat and into the trachea, the large airway from the mouth to the lungs. This is done to ensure that patients who are asleep under anesthesia are able to fully breath. This outcome measured the hours from the time the patient leaves the operating room until they were extubated, or had the tube removed from their trachea.	Hours until patient is extubated from time patient leaves the operating room
Secondary Outcome 5: Patient Controlled Analgesia (PCA) and Oral Opioid Consumption at the 24, 48, 96 and 120 Hour Time Points	Patient Controlled Analgesia (PCA) is when the patient chooses to give themselves some form of analgesia, or painkiller, depending on their post-operation pain levels. Oral opioid consumption is the measure of all painkiller medicine that was prescribed by the hospital to the patient to take. This outcome measures each of these up to each time point and also measures the total PCA and oral opioid consumption post-procedure for the whole hospital stay.	24-, 48, -96 and 120-hours
Secondary Outcome 6: ICU and Hospital Length of Stay From Procedure to Discharge	The outcome measures the time spent in the intensive care unit (ICU) as well as the total hospital length of stay.	Procedure to Discharge
Secondary Outcome 7: Ambulatory Movement During Hospital Stay	Ambulatory Movement, defined as the subjects ability to sit up, stand up, walk and flex both the left and right shoulders, was measured at multiple time points during hospital stay.	Baseline, 48, 72, 96, 120 Hours and Discharge

Collaborators and Investigators

• Sponsor: AtriCure, Inc.
• Investigators: Principal Investigator: Wei Lau, MD, William Beaumont Hospitals

Publications and helpful links

General Publications

• Sepsas E, Misthos P, Anagnostopulu M, Toparlaki O, Voyagis G, Kakaris S. The role of intercostal cryoanalgesia in post-thoracotomy analgesia. Interact Cardiovasc Thorac Surg. 2013 Jun;16(6):814-8. doi: 10.1093/icvts/ivs516. Epub 2013 Feb 19.
• Moorjani N, Zhao F, Tian Y, Liang C, Kaluba J, Maiwand MO. Effects of cryoanalgesia on post-thoracotomy pain and on the structure of intercostal nerves: a human prospective randomized trial and a histological study. Eur J Cardiothorac Surg. 2001 Sep;20(3):502-7. doi: 10.1016/s1010-7940(01)00815-6.
• Glauber M, Karimov JH, Farneti PA, Cerillo AG, Santarelli F, Ferrarini M, Del Sarto P, Murzi M, Solinas M. Minimally invasive mitral valve surgery via right minithoracotomy. Multimed Man Cardiothorac Surg. 2009 Jan 1;2009(122):mmcts.2008.003350. doi: 10.1510/mmcts.2008.003350.
• Loan WB, Dundee JW. The clinical assessment of pain. Practitioner. 1967 Jun;198(188):759-68. No abstract available.
• PAPPER EM, BRODIE BB, ROVENSTINE EA. Postoperative pain; its use in the comparative evaluation of analgesics. Surgery. 1952 Jul;32(1):107-9. No abstract available.
• Katz J. Cryoanalgesia for postthoracotomy pain. Ann Thorac Surg. 1989 Jul;48(1):5. doi: 10.1016/0003-4975(89)90166-5. No abstract available.
• Cook TM, Riley RH. Analgesia following thoracotomy: a survey of Australian practice. Anaesth Intensive Care. 1997 Oct;25(5):520-4.
• SIMPSON BR, PARKHOUSE J, MARSHALL R, LAMBRECHTS W. Extradural analgesia and the prevention of postoperative respiratory complications. Br J Anaesth. 1961 Dec;33:628-41. doi: 10.1093/bja/33.12.628. No abstract available.
• Maiwand MO, Makey AR, Rees A. Cryoanalgesia after thoracotomy. Improvement of technique and review of 600 cases. J Thorac Cardiovasc Surg. 1986 Aug;92(2):291-5.
• Gough JD, Williams AB, Vaughan RS, Khalil JF, Butchart EG. The control of post-thoracotomy pain. A comparative evaluation of thoracic epidural fentanyl infusions and cryo-analgesia. Anaesthesia. 1988 Sep;43(9):780-3. doi: 10.1111/j.1365-2044.1988.tb05757.x.
• Gwak MS, Yang M, Hahm TS, Cho HS, Cho CH, Song JG. Effect of cryoanalgesia combined with intravenous continuous analgesia in thoracotomy patients. J Korean Med Sci. 2004 Feb;19(1):74-8. doi: 10.3346/jkms.2004.19.1.74.
• Lau WC, Shannon FL, Bolling SF, Romano MA, Sakwa MP, Trescot A, Shi L, Johnson RL, Starnes VA, Grehan JF. Intercostal Cryo Nerve Block in Minimally Invasive Cardiac Surgery: The Prospective Randomized FROST Trial. Pain Ther. 2021 Dec;10(2):1579-1592. doi: 10.1007/s40122-021-00318-0. Epub 2021 Sep 20.

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2016
• Primary Completion (Actual): March 4, 2019
• Study Completion (Actual): August 28, 2019

Study Registration Dates

• First Submitted: September 26, 2016
• First Submitted That Met QC Criteria: September 30, 2016
• First Posted (Estimate): October 4, 2016

Study Record Updates

• Last Update Posted (Actual): September 4, 2020
• Last Update Submitted That Met QC Criteria: August 18, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Thoracotomy; Visual Analog Scale (VAS); CryoAnalgesia; Forced Expiratory Volume (FEV1)
• Other Study ID Numbers: CP2015-4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No