Cryoablation of Intercostal Nerves for Post-Operative Pain Management in Opioid-Tolerant Patients

A Randomized Controlled Trial of cryoSPHERE (CRYOS/CRYOS-L) Ablation of Intercostal Nerves for Post-Operative Pain Management in Opioid-Tolerant Patients Undergoing Robotic-Assisted Thoracoscopic Surgery

The main objective study is to compare the use of the cryoSPHERE probe to the standard-of-care method for pain management of patients receiving robotic-assisted thoracoscopic surgery, including reductions in opioid pain medication use and the development of post-surgical morbidity.

Study Overview

• Status: Enrolling by invitation
• Conditions: Pain; Pain, Postoperative
• Intervention / Treatment: Device: cryoSPHERE Ablation; Drug: Bupivacaine

Detailed Description

Patients who take more opioid medications after surgery tend to have longer hospital stays, and they are at risk of developing pneumonia and other postoperative morbidities. Opioid-tolerant patients are at a higher risk of developing these morbidities because they often require higher doses of opioid medications to manage their post-operative pain. Reducing post-operative pain in these patients through non-opioid means helps reduce their risk of developing morbidities, and is potentially a more effective form of pain management, particularly in this patient population.

This is a single-center, prospective cohort registry with a historical control, and an estimated duration of 2 years. This study's primary objective is to evaluate the cryoSPHERE probe for ablation in pain control after surgery (measured using opioid medication). The secondary objectives are the evaluation of morbidities, length of stay, cost, and incidence of neuroma formation.

We plan to recruit 75 patients who will receive the cryoSPHERE probe and compare them to 75 patients who did not receive the cryoSPHERE probe. The experimental group will receive cryoSPHERE ablation of intercostal nerves and liposomal bupivacaine. The historical control group will have had robotic-assisted thoracoscopic surgery and an intercostal nerve block with liposomal bupivacaine and no cyroSPHERE probe.

• Study Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Darrel Cleere, BSN; Phone Number: 713-441-6232; Email: dwcleere@houstonmethodist.org
• Study Contact Backup: Name: Shondra Word; Phone Number: 713-441-5122; Email: sword@houstonmethodist.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Research Institute
      • Contact: Shondra Word; Phone Number: 713-441-5122; Email: sword@houstonmethodist.org
      • Contact: Darrel W Cleere, BSN; Phone Number: 713-515-8380; Email: dwcleere@houstonmethodist.org
      • Principal Investigator: Min Kim, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female patients 18-90 years of age
• Diagnosis requiring robotic-assisted thoracoscopic surgery
• Daily opioid use for at least 30 days consecutively at any point during the last 12 months prior to surgery or using opioids at the time of study enrollment
• Experimental group only: agreement and consent to comply with all aspects of the study protocol and data collection, including follow-up contact.

Exclusion Criteria:

• Previous major surgery at the operative site (thoracotomy)
• Allergy to aluminum
• Allergy to plastics
• Allergy to bupivacaine
• Shingles disease
• Demyelinating illnesses
• Involvement with other interventional studies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nerve Block Using Liposomal Bupivacaine and cryoSPHERE Ablation; The experimental group (75 participants) will undergo intercostal nerve block using liposomal bupivacaine and the cryoSPHERE ablation of intercostal nerves during robotic-assisted thoracoscopic operation at Houston Methodist Hospital.	Device: cryoSPHERE Ablation; The cryoSPHERE probe will be introduced through a thoracoscopic port and placed inferior to each rib level and 2cm lateral and away from the sympathetic chain when clearly visible or 4cm lateral and away from the spine when the sympathetic chain is not visible. Levels to be ablated are intercostal spaces 3-9. Each intercostal nerve will undergo cryogenic ablation of -70 degrees Celsius for 120 seconds. The probe will be firmly pushed against the nerve for 120 seconds and will only be released from the nerve when the probe has thawed. Axons within the intercostal nerve that send pain signals will be destroyed distal to the cryoablation site. However, the tubules structures (epineurium, perineurium, and endoneurium) of the nerve will remain intact, allowing the axons to regenerate and nerve function to resume after one to three months.; Other Names: cryoSPHERE; Drug: Bupivacaine; A long needle will be introduced through a thoracoscopic port, and in each intercostal space (1-11), 1ml of liposomal bupivacaine will be injected onto the intercostal nerves to induce intercostal nerve blockage.; Other Names: Exparel; liposomal bupivacaine
Other: Historical Controls; A total of 75 propensity score-matched historical controls will be selected from the pool of patients who had standard intercostal nerve block using liposomal bupivacaine alone at Houston Methodist Hospital from January 1, 2017 through January 1, 2022, inclusively.	Drug: Bupivacaine; A long needle will be introduced through a thoracoscopic port, and in each intercostal space (1-11), 1ml of liposomal bupivacaine will be injected onto the intercostal nerves to induce intercostal nerve blockage.; Other Names: Exparel; liposomal bupivacaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid Use Within 24 Hours After Chest Tube Removal	Opioid use measured as the daily dose of milligram morphine equivalents (MME)	From the time of chest tube removal to 24 hours after chest tube removal

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Emergent Adverse Effects (TEAE)	Morbidity, defined as total emergent adverse effects (TEAE) for the experimental group vs. control	Time of discharge (up to 1 year after surgery), 5 weeks after surgery, 3 months after surgery, and 6 months after surgery
Length of Hospital Stay	Time spent in the hospital from admission for surgery until discharge or death	From admission to discharge or death, up to 1 year after surgery
Mean Cost of Hospital Care	Total cost of billed medical care for the surgery	From admission to discharge or death, up to 1 year after surgery
Number of Readmissions	The number of readmissions to the hospital	From initial admission for surgery to 28 days after surgery
Neuroma Formation	The formation of a neuroma around the site of nerve block administration	Time of discharge (up to 1 year after surgery), 3 months after surgery, and 6 months after surgery
Pain Score	Patient's perceived pain level on a scale of 1 to 10	Time of discharge (up to 1 year after surgery), 5 weeks after surgery, 3 months after surgery, and 6 months after surgery
PROMIS3a Pain Intensity	Patient's perceived pain level on a scale of 3-15, per PROMIS Pain Intensity Short Form 3a v1.0	Time of discharge (up to 1 year after surgery), 5 weeks after surgery, 3 months after surgery, and 6 months after surgery
PROMIS8a Pain Interference	Patient's perceived pain interference level on a scale of 8-40, per PROMIS Pain Interference Adult Form	Time of discharge (up to 1 year after surgery), 5 weeks after surgery, 3 months after surgery, and 6 months after surgery
Opioid Use after Surgery	Mean daily opioid use after surgery measured in milligram morphine equivalents (MME)	Day 1 after surgery, day 3 after surgery, 5 weeks after surgery, 3 months after surgery

Collaborators and Investigators

• Sponsor: The Methodist Hospital Research Institute
• Investigators: Principal Investigator: Min Kim, MD, The Methodist Hospital Research Institute

Publications and helpful links

General Publications

• Rice DC, Cata JP, Mena GE, Rodriguez-Restrepo A, Correa AM, Mehran RJ. Posterior Intercostal Nerve Block With Liposomal Bupivacaine: An Alternative to Thoracic Epidural Analgesia. Ann Thorac Surg. 2015 Jun;99(6):1953-60. doi: 10.1016/j.athoracsur.2015.02.074. Epub 2015 Apr 23.
• Goto T. What is the best pain control after thoracic surgery? J Thorac Dis. 2018 Mar;10(3):1335-1338. doi: 10.21037/jtd.2018.03.63. No abstract available.
• Nobel TB, Adusumilli PS, Molena D. Opioid use and abuse following video-assisted thoracic surgery (VATS) or thoracotomy lung cancer surgery. Transl Lung Cancer Res. 2019 Dec;8(Suppl 4):S373-S377. doi: 10.21037/tlcr.2019.05.14. No abstract available.
• Brown LM, Kratz A, Verba S, Tancredi D, Clauw DJ, Palmieri T, Williams D. Pain and Opioid Use After Thoracic Surgery: Where We Are and Where We Need To Go. Ann Thorac Surg. 2020 Jun;109(6):1638-1645. doi: 10.1016/j.athoracsur.2020.01.056. Epub 2020 Mar 3.
• Kim MP, Chan EY, Meisenbach LM, Dumitru R, Brown JK, Masud FN. Enhanced recovery after thoracic surgery reduces discharge on highly dependent narcotics. J Thorac Dis. 2018 Feb;10(2):984-990. doi: 10.21037/jtd.2018.01.99.
• AtriCure, I., croSPHERE Probe Package Insert.
• Graves CE, Moyer J, Zobel MJ, Mora R, Smith D, O'Day M, Padilla BE. Intraoperative intercostal nerve cryoablation During the Nuss procedure reduces length of stay and opioid requirement: A randomized clinical trial. J Pediatr Surg. 2019 Nov;54(11):2250-2256. doi: 10.1016/j.jpedsurg.2019.02.057. Epub 2019 Mar 17.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Anticipated): March 15, 2025
• Study Completion (Anticipated): September 15, 2025

Study Registration Dates

• First Submitted: February 14, 2022
• First Submitted That Met QC Criteria: March 2, 2022
• First Posted (Actual): March 11, 2022

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: nerve block; bupivacaine; length of stay; pain management; neuroma; pulmonary surgical procedures; robotic surgical procedures; pneumonectomy; analgesics, opioid; drug tolerance
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: PRO00029370

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.: Yes