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

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
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

Conditions
-----------------
Pain, Pain, Postoperative

Intervention / Treatment
-----------------
* Device: cryoSPHERE Ablation
* Drug: Bupivacaine


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nerve Block Using Liposomal Bupivacaine and cryoSPHERE Ablation<br>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<br>* 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.<br>* Other names: cryoSPHERE;Drug: Bupivacaine<br>* 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.<br>* Other names: Exparel;|
| Other: Historical Controls<br>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<br>* 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.<br>* Other names: Exparel;|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pain management, pulmonary surgical procedures, robotic surgical procedures, pneumonectomy, nerve block, neuroma, analgesics, opioid, bupivacaine, length of stay, drug tolerance