Genicular Radiofrequency Ablation Following Total Knee Arthroplasty

Study Overview
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Brief Summary
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Currently, nearly 1 million total knee arthroplasties (TKA) are performed yearly in the United States. Three million are projected to be performed in 2040. Between 15-30% of all patients who undergo TKA have continued pain, reduced quality of life and functional impairments that cannot be attributed to hardware failure/loosening or infection. Treatment options for persistent post TKA pain (failed TKA) are limited. There is a need for minimally invasive, and effective pain and disability modulating interventions for patients with failed TKA. Genicular radiofrequency ablation (GRFA) has been described, refined, and validated as an effective minimally invasive intervention to control refractory knee pain secondary to knee osteoarthritis (OA) as evidenced by three favorable meta-analyses published in 2021 alone.3-5 GRFA is a minimally invasive percutaneous procedure that utilizes thermal energy to coagulate nerves from the knee. Though sometimes used in practice, there is limited research describing and evaluating GRFA for patients with failed TKA. This will be the first trial to evaluate the safety and efficacy of GRFA in patients with failed TKA using a robust study design and up-to-date, evidence-based selection criteria and technique.

Detailed Description
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The general objective of this study is to determine the safety and efficacy of GRFA in patients with failed TKA. The central hypothesis is that GRFA is safe and more efficacious in improving pain and function than sham GRFA. A triple blinded randomized sham-controlled trial design will be used. Patients with failed TKA will be recruited and randomized into either a thermal or sham GRFA group. Patient selection criteria and GRFA procedural technique will incorporate refinements based on expanded understanding from recent research. Outcomes will be assessed prior to and at 3, 6 and 12 months post-GRFA. The primary outcome measures will be change in pain (NRS). Secondary outcomes will include safety and changes in function (WOMAC; sit-stand test; strength; range of motion & balance), participants' impression of change, perceived need for revision arthroplasty, analgesic use, and quality-of-life. Crossover will be offered to participants in the sham group at 6 months post-treatment. Data will be analyzed using descriptive, linear mixed-effects model and Kaplan-Meier Survival Curve statistics. The proposed research is innovative and important as it uses a robust study design to evaluate the safety and efficacy of an emerging RFA intervention in a prevalent suffering patient population.

Official Title
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The Safety and Efficacy of Genicular Radiofrequency Ablation for Patients With Persistent Knee Pain Following Total Knee Arthroplasty - A Triple Blinded Randomized Sham-Controlled Trial

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Procedure: Genicular Radiofrequency Ablation
* Procedure: Sham Genicular Radiofrequency Ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >1 year post TKA persistent knee pain > 4/10 in intensity on average over the prior week of one of the post-TKA knees refractory to conventional treatment (i.e., physiotherapy, medication, etc.) ≥80% pain relief with a single fluoroscopically guided local anesthetic block using 0.5 mL of 2% lidocaine for the medial and lateral branches of the nerve to the vastus intermedialis, nerve to the vastus lateralis*, inferior medial genicular nerve, infrapatellar branch of the saphenous nerve, and the recurrent fibular nerve. 0.5 mL will be injected over 2 spots (1.5 cm apart) for each of the superior medial and lateral genicular nerves corresponding to the sites of the RF cannulae for the bipolar strip lesions. *Blocks will be combined fluoroscopy/ultrasound guided. Exclusion Criteria: Infection (peri-prosthetic, joint, systemic, skin/soft tissue overlying the knee to be treated) Prosthetic loosening or failure, periprosthetic fracture Severe psychiatric disorder Non-genicular lower extremity pain source from the spine (i.e., radiculopathy or neurogenic claudication) or peripheral joints (i.e., hip osteoarthritis) Peripheral vascular disease causing vascular claudication Connective tissue/inflammatory joint disease/widespread soft tissue pain disorder Poor tolerance of injection procedures (as observed from the prognostic local anesthetic blocks) Allergy to local anesthetic, synovial expansion into the anticipated path(s) of the local anesthetic needle/RF cannula as determined by ultrasound scanning Uncontrolled bleeding diathesis Pregnancy Pacemaker or neurostimulator Inability to complete Patient-Reported Outcome Measures due to cognitive or language limitations.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 (GRFA)<br>After the cannulae are placed and tines deployed, a single lesion (30 second ramp-up time; 80C x 2 minutes) will be made at each of the medial and lateral branches of the nerve to the vastus intermedialis, nerves to the vastus lateralis and medialis, recurrent fibular nerve, inferior medial genicular nerve. One bipolar strip lesion (intercannula distance 1.5 cm; anticipated strip lesion length 2.0 cm) at the superior medial and lateral genicular nerves will be made to accommodate anatomical variability. | Procedure: Genicular Radiofrequency Ablation<br>* After the cannulae are placed and tines deployed, a single lesion (30 second ramp-up time; 80C x 2 minutes) will be made at each of the medial and lateral branches of the nerve to the vastus intermedialis, nerves to the vastus lateralis and medialis, recurrent fibular nerve, inferior medial genicular nerve. One bipolar strip lesion (intercannula distance 1.5 cm; anticipated strip lesion length 2.0 cm) at the superior medial and lateral genicular nerves will be made to accommodate anatomical variability.<br>|
| Active Comparator: Group 2 (Sham)<br>The same procedure will be employed as per Group 1 - However, the sham procedure will involve no electrical signal applied to the participant. | Procedure: Sham Genicular Radiofrequency Ablation<br>* After the cannulae are placed and tines deployed, a single lesion (no electrical signal applied to patient) will be made at each of the medial and lateral branches of the nerve to the vastus intermedialis, nerves to the vastus lateralis and medialis, recurrent fibular nerve, inferior medial genicular nerve. One bipolar strip lesion (intercannula distance 1.5 cm; anticipated strip lesion length 2.0 cm) at the superior medial and lateral genicular nerves will be made to accommodate anatomical variability.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Pain Intensity Over the Prior week (0 - 10) | Numerical pain rating scale (0 - 10) with higher scores indicating a worse outcome | 6 months | 
| Change in pain intensity between pre- and 6-months post-intervention | Numerical Pain rating scale (NPRS) 6 month minus NPRS pre-intervention, with increased negative scores indicating a better outcome | 6 months | 
| Proportion of participants exceeding 50% pain relief | Proportion of participants that experience ≥ 50% pain relief | 6 months | 
| Proportion of participants exceeding Minimal Clinically Important Difference (MCID) pain relief | Proportion of participants that experience MCID knee pain relief | 6 months | 
| Safety - Adverse Events | Presence of self-reported complications | 1-week, 3, 6 and 12-months post-intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Pain Intensity Over the Prior Week (0 - 10) | Numerical pain rating scale (0 - 10) with higher scores indicating worse outcomes | 3 and 12-months post-intervention | 
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Measure of pain (0 - 20), stiffness (0 - 8) and physical function (0 - 68) with higher scores indicating wore pain, stiffness and functional limitations | 3, 6 and 12-months post-intervention | 
| The Clinical Global Impressions Scale (CGI) | Patient reported global impression of change (1 = Very Much Improved to 7 = Very Much Worse) | 3, 6 and 12-months post-intervention | 
| Perceived Need for Revision Arthroplasty | If revision surgery of your knee replacement was available to you, how interested would you be in having it at this time? Y or N | Baseline (Prior to), 3, 6 and 12-months post-intervention | 
| Analgesic Use | Quantitative Analgesic Questionnaire | Baseline (Prior to), 3, 6 and 12-months post-intervention | 
| Health-related Quality of Life | EQ-5D-5L | Baseline (Prior to), 3, 6 and 12-months post-intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genicular Radiofrequency Ablation, Randomized Controlled Trial, Knee Pain, Balance