FROST-STERN Trial: A Trial of Intraoperative Cryoablation for Post Operative Pain Management After Full Sternotomy (FROST-STERN)

FROST-STERN: Functional Recovery and Opioid Sparing Technique for STERNotomy A Randomized Trial of Intraoperative Intercostal Cryoablation for Postoperative Pain Management Following Full Sternotomy

Background and Rationale: Open-heart surgery via a median sternotomy is associated with severe acute postoperative pain. This pain can impair a patient's ability to take deep breaths and cough effectively which increases the risk of postoperative lung complications such as atelectasis (collapsed lung) or pneumonia. Traditional pain management protocols rely heavily on opioid medications, which carry systemic side effects including respiratory depression, sedation, and nausea. While short-acting regional nerve blocks are helpful, their effects often wear off within the first 24 hours. The result is a suboptimal duration of pain relief for the remaining critical early recovery window. Intra-operative intercostal nerve cryoablation (temporary nerve freezing) offers a prolonged, localized, and non-opioid alternative. By temporarily interrupting pain signals along the chest wall, this technique may preserve early respiratory function and reduce systemic narcotic requirements during acute recovery.

Study Objective:The objective of this study is to evaluate whether adding bilateral intra-operative intercostal nerve cryoablation (levels T2 through T6) improves the recovery of pulmonary function and reduces acute pain in patients undergoing elective cardiac surgery via a full median sternotomy.

Study Design:This is a prospective, randomized, double-blind, sham-controlled, single-center trial. A total of 100 adult patients scheduled for elective first-time cardiac surgery (such as coronary artery bypass grafting or valve replacement) will be randomized in a 1:1 ratio into either an intervention or control group.

Intervention Group: Patients will receive bilateral intraoperative intercostal nerve cryoablation at levels T2-T6 from within the surgical field prior to sternal closure.

Control Group: Patients will receive standard-of-care multimodal analgesia. Patients, clinical staff managing postoperative care, and data assessors will be fully blinded to the treatment assignment.

Primary Outcome:Pulmonary Function Recovery (FEV1 and Incentive Spirometry): Measured as the percentage of the patient's preoperative baseline Forced Expiratory Volume in 1 second (FEV1) and incentive spirometry recovered at 48 hours postoperatively.

Key Secondary Outcomes:

Cumulative postoperative opioid consumption (measured in Morphine Milligram Equivalents, or MME) during the first 72 hours.

Subjective pain intensity scores at rest and during deep inspiration/coughing (using a 0-10 Numerical Rating Scale) at 12, 24, 48, and 72 hours.

Key recovery milestones, including time to first extubation, intensive care unit (ICU) length of stay, and total hospital length of stay.

Incidence of long-term or chronic post-sternotomy pain syndrome at 3 and 6 months follow-up.

Study Overview

• Status: Not yet recruiting
• Conditions: Postoperative Pain; Pulmonary Dysfunction; Median Sternotomy Recovery
• Intervention / Treatment: Device: Intercostal Nerve Cryoablation

Detailed Description

FROST-STERN Research Protocol

1. Study Rationale and Background Median sternotomy remains the gold standard surgical approach for complex open-heart surgeries, including coronary artery bypass grafting (CABG) and valve replacements. However, it is inherently associated with severe acute and chronic postoperative pain. Approximately 28% of patients experience chronic post-sternotomy pain, with 4% characterizing it as severe.

   Inadequate acute pain management often results in patient "splinting" and impaired respiratory effort. This poor bronchopulmonary hygiene significantly increases the risks of acute postoperative lung complications, such as atelectasis and pneumonia, which can extend intensive care unit (ICU) and hospital length of stay (LOS). The pathophysiology of this pain stems from direct surgical trauma to peripheral nerve pathways, traction-induced brachial plexus injury, and intercostal neuralgia resulting from internal mammary artery harvesting.

   While traditional pain protocols rely heavily on systemic opioids, high narcotic burdens carry substantial side effects, including respiratory depression, sedation, and ileus. Traditional regional plane blocks offer relief that lasts only hours rather than months. This trial introduces intraoperative intercostal nerve cryoablation (INC) into a standardized cardiac Enhanced Recovery After Surgery (ERAS) pathway. By utilizing extreme cold to induce temporary, reversible Wallerian degeneration, INC offers a localized, non-addictive, long-acting analgesic solution designed to reduce early postoperative opioid reliance and accelerate the recovery of objective pulmonary function.

2. Participant Recruitment, Screening, and Consent Potential subjects will be identified and recruited from the Cardiac Surgery Clinic (outpatients) or the Inpatient Cardiac Surgery Service days to weeks prior to their scheduled operation.

   • Screening: The Principal Investigator (PI) or a designated Study Nurse will review patients' electronic medical charts against strict eligibility criteria.
   • Consent Process: Eligible patients will be approached in a private clinic room or at their hospital bedside. The study team will spend 5 to 10 minutes presenting the trial, emphasizing its voluntary nature. Patients will be provided with the written Informed Consent Form (ICF) to read over. Ample time will be provided to answer all questions. To verify comprehension prior to signing, the investigator will ask the patient several validating questions about the study. Once consent is obtained, it will be documented via a formal clinical note in the patient's medical record, and a copy of the ICF will be given to the participant.

3. Randomization, Allocation, and Blinding The FROST-STERN trial is a prospective, randomized, double-blind, parallel-group, sham-controlled trial with a target enrollment of 100 subjects.

   • Allocation: Randomization will be executed in blocks of 10 (5 ERAS-only and 5 ERAS+INC). Prior to surgery, designated study staff who are entirely independent of post-operative patient assessments will draw 1 of 10 sequentially numbered, sealed opaque envelopes to determine the group assignment.
   • Blinding: The independent staff member will communicate the assignment directly to the operating surgeon. The patient, post-operative clinical teams, intensive care staff, and data assessors will remain completely blinded to the treatment arm throughout the duration of the trial.

4. Intraoperative Intervention Protocol All surgeries will be performed according to standard institutional care. The active study intervention takes place after the patient has been safely decannulated from cardiopulmonary bypass (CPB) and surgical hemostasis has been fully achieved, but before the placement of sternal wiring.

   • Experimental Arm (Cryoablation Group): Under direct internal visualization from within the open mediastinum/pleural space, the attending cardiothoracic surgeon will apply a specialized cryo-anesthesia probe directly to the intercostal neurovascular bundles. Bilateral treatment will be delivered across five distinct dermatomal levels: T2 through T6. Each individual nerve bundle will undergo an ablation cycle lasting 60 to 90 seconds at an operating temperature between -50 degrees Celsius and -70 degrees Celsius to induce temporary nerve conduction block.
   • Active Comparator Arm (Control Group): Patients assigned to the control group will receive the institutional standard of care, which involves standard multimodal analgesia and regional thoracic plane blocks utilizing bupivacaine infiltration. To preserve the double-blind architecture, surgeons may perform a sham application by placing the unactivated cryoprobe against the designated anatomical landmarks without delivering thermal energy.

5. Postoperative Management and Rescue Analgesia

   To ensure patient safety, a strict, standardized multimodal rescue analgesia framework is mandated across both study arms to ensure no patient is left with unmanaged breakthrough pain:

   • First-Line Therapy: Scheduled Acetaminophen (e.g., 1000mg IV or PO every 6 hours).
   • Second-Line Therapy: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), provided there are no clinical contraindications related to renal function or active bleeding risks.
   • Third-Line (Breakthrough Rescue): Opioid Patient-Controlled Analgesia (PCA) using either Hydromorphone or Fentanyl programmed with a fixed, standardized lockout interval.

6. Primary and Secondary Endpoint Assessments Data collection spans from the baseline pre-operative clinic visit through a 3-month follow-up window.

   • Primary Endpoint: The percent recovery of Forced Expiratory Volume in 1 second (FEV1) and volumetric incentive spirometry at 48 and 72 hours postoperatively. This is calculated as a direct ratio comparing the absolute values (measured in liters) obtained on Postoperative Days (POD) 2 and 3 against the patient's preoperative baseline values. Bedside testing will be facilitated by trained research or respiratory staff using a standard sternal stabilization pillow to mitigate incisional strain.
   • Secondary Pain Intensity: Visual Analog Scale (VAS) pain scores (0 to 10 integer scale, where 0 = no pain and 10 = worst imaginable pain) captured dynamically during the performance of incentive spirometry at the day of extubation, 48 hours, and 72 hours.
   • Secondary Opioid Consumption: Cumulative systemic narcotic use recorded every 24 hours up to 72 hours, mathematically converted into total Morphine Milligram Equivalents (MME).
   • Secondary Recovery Milestones: Granular tracking of time to first extubation (measured in hours from surgery end), time to first independent ambulation (hours), and total length of stay (LOS) within both the ICU and general hospital wards (tracked in hours, divided by 24 for final day-count reporting).
   • Secondary Safety Endpoints: Tracking the cumulative incidence of procedure-related complications through the follow-up period, specifically focusing on pneumothorax, prolonged intercostal neuralgia, or localized skin numbness.
   • Secondary Chronic Pain: At the 3-month post-operative mark, patients will be contacted via telephone or an outpatient clinic visit to complete the Brief Pain Inventory Short Form (BPI-SF) and the SF-12 health survey. The BPI-SF will specifically capture pain severity (0-10 scale), pain interference with daily activities (0-10 scale), and perceived percentage of pain relief (0% to 100%).
7. Statistical Plan and Sample Size Justification The study is powered at 90% (with a significance level alpha = 0.05) to detect a statistically and clinically meaningful 15% improvement in baseline FEV1 values and a concurrent 30% reduction in total MME requirements in the cryoablation cohort compared to controls. Factoring in an anticipated post-operative attrition rate of 20% to 25% due to technical or clinical variances, the final sample size is set at 100 patients split equally between the two arms.

Continuous variables (such as FEV1, MME, LOS hours, and VAS scores) will be assessed for normality. Normally distributed continuous data will be analyzed using parametric independent t-tests, while skewed continuous data will be evaluated using the non-parametric Mann-Whitney U test. Categorical safety outcomes and complication rates will be compared utilizing Chi-squared tests or Fisher's exact tests. To account for baseline variances in pulmonary function, primary endpoints will be formally evaluated using an Analysis of Covariance (ANCOVA) model, integrating baseline pre-operative FEV1 as a continuous covariate. Paired t-tests will be applied to assess longitudinal changes in individual baseline-to-3-month BPI-SF and SF-12 scores. All raw endpoints will be managed securely within a blinded REDCap database environment.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ricardo Verdiner, M.D.; Phone Number: 732-235-6155; Email: ricardo.verdiner@rutgers.edu
• Study Contact Backup: Name: Danielle Plyler; Phone Number: 732-2356284; Email: plylerde@rutgers.edu

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers University Robert Wood Johnson University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age: Adults aged 40 and above no upper limit.
• Surgical Plan: Undergoing first-time elective cardiac surgery via full median sternotomy (e.g., CABG, AVR, MVR).
• Cognitive Status: Ability to understand and provide informed consent and utilize a Numerical Rating Scale (NRS) for pain.
• Baseline Pain: Preoperative chronic pain score of < 3/10.

Exclusion Criteria:

• Redo Sternotomy: Previous cardiac surgery (due to adhesions and altered anatomy).
• Opioid Tolerance: Preoperative daily opioid use for >4 weeks (to avoid confounded MME requirements).
• Neurological Conditions: Pre-existing intercostal neuralgia, peripheral neuropathy, or significant psychiatric disorders.
• Emergency Cases: Hemodynamically unstable patients or those requiring emergency "crash" surgery.
• Allergies: Known hypersensitivity to local anesthetics (if used in the control arm).
• Anatomical Barriers: Severe chest wall deformities or extensive pleural adhesions.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intercostal Nerve Cryoablation Group; Patients in this group receive the active treatment-intraoperative bilateral intercostal nerve cryoablation (levels T2-T6) before the chest is closed.	Device: Intercostal Nerve Cryoablation; This is cryoablation of intercostal nerves after median sternotomy (an opioid sparing technique) to reduce post operative pain past 48hrs.; Other Names: cryoneurolysis
No Intervention: Control Group; Patients in this group receive standard post-operative pain management.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1 Comparison to Baseline	Percent recovery of Forced Expiratory Volume in one second (FEV1) measured in liters at day of extubation, 48, and 72 hours postoperatively. The final values will be measured as the ratio of the Postoperative extubation day 1, day 2, and day 3 volumes to the preoperative baseline FEV1 results. (e.g. POD3 FEV1 Volume/Baseline FEV1 Volume= Percent Recovery POD 3 FEV1,.... etc)	After Extubation day 1-3
Incentive Spirometery Comparison to Baseline	The percent recovery of volumetric Incentive Spirometry at day of extubation, 48 and 72 hours post operatively. This is calculated as a direct ratio comparing the absolute values (measured in liters) obtained on Postoperative Days (POD) 2 and 3 against the patient's preoperative baseline values (e.g. POD2 IS Volume/IS Baseline Volume=Percent Recovery POD 2 IS). Bedside testing will be facilitated by trained research or respiratory staff using a standard sternal stabilization pillow to mitigate incisional strain.	After extubation day 1- 3.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery Milestones (Extubation)	Granular tracking of time to first extubation (measured in hours from surgery end).	This will be documented in terms of hours from end of original surgery.
Recovery Milestone (Ambulation)	Time to first independent ambulation (hours) from end of surgery.	Hours from end of surgery.
Pain Intensity	Visual Analog Scale (VAS) during incentive spirometry at day of extubation, day 2 and day 3 (POD 2 and 3). Visual Analog Scale (VAS) pain scores (0 to 10 integer scale, where 0 = no pain and 10 = worst imaginable pain) captured dynamically during the performance of incentive spirometry at the day of extubation, day 2 and day 3.	After extubation day 1-3
Opioid Consumption	Cumulative systemic narcotic use recorded every 24 hours up to 72 hours, mathematically converted into total Morphine Milligram Equivalents (MME).	Postoperatively after extubation day 1-3.
Chronic Pain	Incidence Post-Traumatic Sternotomy Pain Syndrome at 3 months (via Brief Pain Inventory). At the 3-month post-operative mark, patients will be contacted via telephone or an outpatient clinic visit to complete the Brief Pain Inventory Short Form (BPI-SF) and the SF-12 health survey. The BPI-SF will specifically capture pain severity (0-10 scale), pain interference with daily activities (0-10 scale), and perceived percentage of pain relief (0% to 100%).	Postoperatively 3 months after day of surgery
Safety (Incidence of Complications)	Incidence of procedure-related complications (e.g., pneumothorax, neuralgia, or localized skin numbness). Tracking the cumulative incidence of procedure-related complications through the follow-up period, specifically focusing on pneumothorax, prolonged intercostal neuralgia, or localized skin numbness.	From day of surgery until the date of first documented progression, assessed up to 3 months after surgery.
Recovery Milestone (Length of ICU Stay)	Total length of stay (LOS) within the ICU (tracked in hours after end of surgery, divided by 24 for final day-count reporting).	Tracked in hours after end of surgery until discharge out of ICU to step-down.
Recovery Milestone (Total Hospital Stay)	Tracked in hours after end of surgery until discharged out of the hospital and then divided by 24 for final day-count reporting.	End of surgery until discharged out of the hospital.

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: AtriCure, Inc.
• Investigators: Principal Investigator: Ricardo Verdiner, M.D., Rutgers University

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: May 29, 2026
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: cardiac surgery; CABG; post operative pain; FEV1; cryoablation; allodynia; cryoanalgesia; nerve regeneration; cryoneurolysis; intercostal nerve block; cardiac valve replacement; median sternotomy; nonopioid analgesia; enhanced recovery after surgery ERAS; MME; Opioid Sparing Effect; Post surgical neuralgia; chronic post sternotomy pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Sensation Disorders; Somatosensory Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Hyperalgesia
• Other Study ID Numbers: Pro2026000975

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data that underlie the results reported in the primary publication (including demographic characteristics, baseline and postoperative FEV1 measurements, and cumulative 72-hour morphine milligram equivalents) will be made available to qualified secondary researchers. Data will only be shared to achieve the aims of an approved methodologically sound scientific proposal. Requesting researchers must sign a formal Data Use Agreement (DUA) and secure independent IRB approval if required by their home institution.
• IPD Sharing Time Frame: Data will become available beginning 6 months after the primary publication of the trial results and will remain accessible for up to 3 years following publication.
• IPD Sharing Access Criteria: Proposals should be directed via email to the Principal Investigator. To gain access, data requestors must submit a formal research protocol detailing the predefined hypotheses and statistical analysis plan. The proposal will be vetted by the trial's steering committee. Approved requestors will be required to sign a standard institutional Data Use Agreement prior to secure data transfer.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

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