Cryoneurolysis Prior to Total Knee Arthroplasty (CRYO-TKA Trial) (CRYO-TKA)

Association of Pre-operative Genicular Nerves Cryoneurolysis With Improved Pain and Function in Patients Undergoing Total Knee Arthroplasty

Approximately 20-30% of patients experience persistent pain after a Total Knee Arthroplasty (TKA). This study investigates whether percutaneous cryoneurolysis of genicular nerves can reduce pain and improve physical function when performed at least 24 hours before surgery. Participants will be randomized to receive either the cryoneurolysis procedure + TKA or TKA only. Results will be tracked for 6 months to see if the intervention improves long-term recovery and quality of life.

Study Overview

• Status: Recruiting
• Conditions: Chronic Pain; Arthroplasty; Knee Arthroplasty, Total; Knee Arthritis Osteoarthritis; Replacement Material; Genicular Nerves
• Intervention / Treatment: Procedure: CT-guided Cryoneurolysis of the Genicular Nerves

Detailed Description

The current study is a prospective, single-center, randomized comparative trial (1:1 ratio). In the intervention group, cryoneurolysis is performed under imaging guidance targeting the upper lateral and medial and the lower medial genicular nerves. Under prophylactic antibiosis, and imaging guidance 17Gauge cryoprobes will be percutaneously placed at the level of the upper lateral and medial and the lower medial genicular nerves. The final position of each cryo probe will be verified with imaging guidance. Cryoneurolysis protocol will be 5min freezing-4min passive thawing-5min freezing. Post-interventional imaging will verify lack of potential immediate complications

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

Contacts and Locations

• Study Contact: Name: Dimitrios Filippiadis, MD, PhD, EBIR, MSc; Phone Number: +306948513104; Email: dfillipiadis@yahoo.gr
• Study Contact Backup: Name: Vasileios Balomenos, MD, MSc, PhD(c); Phone Number: +30645297496; Email: balomenosv@gmail.com

Study Locations

• Greece
  • Athens, Greece, 12462
    • Recruiting
    • Attikon University General Hospital
    • Contact: Vasileios Balomenos, MD, MSc, PhD(c); Phone Number: +306945297496; Email: balomenosv@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adults ≥18 years undergoing primary TKA for osteoarthritis.
• Cognitively normal and able to self-assess pain and function.
• Provide written informed consent.

Exclusion Criteria:

• Cancer-related knee pain.
• Neurological, psychiatric, or medical conditions interfering with assessment.
• Chronic opioid users.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cryoneurolysis + TKA Arm; CT-guided cryoneurolysis of upper medial, upper lateral, and lower medial genicular nerves ≥24 hours before TKA.	Procedure: CT-guided Cryoneurolysis of the Genicular Nerves; Percutaneous CT-guided cryoneurolysis using up to three cryoprobes (-20°C to -100°C) for temporary sensory nerve interruption.
No Intervention: Control Arm; Standard total knee arthroplasty without preoperative cryoneurolysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pain severity	Change in pain severity (Brief Pain Inventory-BPI) - Baseline to 1 month postoperatively. The BPI typically assesses two primary domains using a 0 to 10 numerical rating scale: Pain Intensity: Patients rate their pain at its "worst," "least," and "average" over the last 24 hours, as well as their pain "right now." 0 = No Pain 10 = Pain as bad as you can imagine Pain Interference: Patients rate how much their pain interferes with seven daily activities (General Activity, Mood, Walking Ability, Normal Work, Relations with others, Sleep, and Enjoyment of Life). 0 = Does not interfere 10 = Completely interferes Because higher numbers represent more intense pain and more significant disruption to life, a reduction in score over time is the goal of most clinical treatments.	1 month postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee Injury and Osteoarthritis Outcome Score	The Knee Injury and Osteoarthritis Outcome Score is a 42-item questionnaire designed to assess short-term and long-term consequences of knee injury. It covers five subscales: Pain, Symptoms, ADL, Sport/Rec, and QOL. Each subscale is transformed to a 0 to 100 scale. Unlike pain-only scales, higher scores mean a better outcome, with 100 representing a perfectly functional knee and 0 representing extreme knee problems.	3 and 6 months post-op
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)	The Western Ontario and McMaster Universities Osteoarthritis Index is the "gold standard" for evaluating patients with hip and knee osteoarthritis. It measures 24 items divided into pain, stiffness, and physical function. Using a Likert scale (0-4 per item), the total score ranges from 0 to 96. For the WOMAC, higher scores mean a worse outcome, reflecting increased pain and significant physical disability.	3 and 6 months post-op
The Cardiovascular and Interventional Radiological Society of Europe (CIRSE) Classification System	The Cardiovascular and Interventional Radiological Society of Europe (CIRSE) Classification System is a tool used by clinicians to standardize the reporting of complications in interventional radiology. It ranks adverse events from Grade 1 to Grade 6. A Grade 1 signifies a minor issue with no therapy required, while a Grade 6 indicates patient death. Therefore, higher scores mean a worse outcome, representing a higher severity of medical complications.	6 months post-op

Collaborators and Investigators

• Sponsor: Attikon Hospital

Publications and helpful links

General Publications

• Dasa V, Larijani GE, Kostajny B, et al. Percutaneous freezing of genicular nerves (cryoneurolysis) for pain management after total knee arthroplasty. Knee. 2016;23(3):523-528. doi:10.1016/j.knee.2016.01.015.
• Ashoorion V, et al. Predictors of persistent post-surgical pain following total knee arthroplasty: a systematic review and meta-analysis. Pain Med. 2023;24(4):369-381. doi:10.1093/pm/pnac144.
• Filippiadis D, Efthymiou E, Tsochatzis A, Kelekis A, Prologo JD. Percutaneous cryoanalgesia for pain palliation: current status and future trends. Diagn Interv Imaging. 2021;102(5):273-278. doi:10.1016/j.diii.2020.11.007.
• Mont MA, Mihalko WM, Chahal J, et al. Cryoneurolysis Associated With Improved Pain, Function, and Sleep in Patients Following Total Knee Arthroplasty. J Arthroplasty. 2025;40(1):92-101. doi:10.1016/j.arth.2024.05.035.

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: February 6, 2026
• First Submitted That Met QC Criteria: February 19, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 19, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Interventional Radiology; Cryoneurolysis; Pain Management; Post-operative recovery
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Chronic Pain; Agnosia
• Other Study ID Numbers: 499

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data will be available upon reasonable request following publication of primary results.
• IPD Sharing Time Frame: IPD and supporting information will be available from June 1st, 2026. End date has not beed decided yet.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No