RFA or Chemical Neurolysis of the Genicular Nerves Compared to Conservative Treatment for Knee Pain Caused by OA

Study Overview
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Brief Summary
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A randomised controlled triall (RCT) with three parallel arms comparing the functional outcome of chemical ablation with phenol and radiofrequency ablation (RFA) of the genicular nerves with conservative treatment in patients with chronic knee pain caused by osteoarthritis (OA).

Detailed Description
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In guidelines for knee osteoarthritis (OA), conservative treatments are physical therapy, analgesics and intra-articular injections with corticosteroids. In severe OA and persisting symptomatic cases the golden standard is joint replacing surgery. A less invasive technique is ablation of the sensory (genicular) nerves of the knee. This technique is beneficial for younger patients as a bridge to surgery or patients that cannot undergo total knee arthroplasty (TKA) due to comorbid health conditions. Nerve ablation can either be done with chemical agents or thermal energy. Although there are numerous studies on genicular nerve block for chronic knee pain caused by OA, there are just a few small studies that compare genicular nerve block with conservative treatment.To be able to determine if genicular nerve ablation is efficacious to serve the gap between conservative treatment and TKA, this randomised controlled trial (RCT) compares two forms of genicular nerve ablation (radiofrequency and phenolisation; intervention) with conservative treatment (control) up to 6 months after treatment.

Official Title
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Patients With Knee Pain Caused by Osteoarthritis: Comparison of Conservative Medical Management With RadioFrequency Ablation or Chemical Neurolysis of the Genicular Nerves With Phenol

Conditions
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Osteo Arthritis Knee, Knee Pain Chronic

Intervention / Treatment
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* Procedure: Diagnostic genicular nerve block
* Procedure: Genicular nerve block with Radiofrequency Ablation (RFA)
* Procedure: Genicular nerve block with Phenol 6%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients of both sexes, >35 years who are not a candidate for TKA due to young age, old age, comorbidity or technical reasons. OKS < 30 on a scale from 0 (severe function) to 48 points (satisfactory function). Continued pain in the target knee that is moderate to severe (defined as NRS ≥ 6 on an 11-point NRS scale) either constantly or with motion despite at least 3 months of conservative treatments. Conservative treatment can include: active physiotherapy, pharmacological treatment of pain (acetaminophen or NSAIDs) and intra-articular corticosteroid infiltration. Radiologic confirmation of arthritis for the target knee. Defined as the Kellgren Lawrence (KL) score of 2 or more on X-ray or MRI. Exclusion Criteria: Patient with prior ablation of the genicular nerves, prior partial, resurfacing, or TKA of the target knee (residual hardware). Patient with a history of neurovascular injury or recent trauma of the lower extremities. Patient with chronic widespread pain. Polyneuropathy and/or radicular pain in the lower extremities. Patient is currently implanted with a neurostimulator. Local or systemic infection (bacteraemia). Uncontrolled immune suppression. Intra-articular injections (steroids, hyaluronic acid, platelet enriched plasma, stem cell, …) in the target knee within 90 days from randomisation. Arthroscopic debridement/lavage into the target knee within 180 days from randomisation. BMI<18,5 kg/m2 and patients with minimal subcutaneous tissue thickness that would not accommodate ablation with phenol or radio frequency (risk of skin burns). Allergies to products used during the procedure (lidocaine, phenol, contrast dye). Patients who have a planned TKA in the near future, defined as patients who already have agreed on a date for the TKA procedure. Patients with psychosocial problems as determined by the investigator.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 90 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: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Chemical ablation of the genicular nerves with Phenol 6%<br>Chemical ablation with phenol is done by injection of 1,5ml of phenol 6 % at the superomedial, the superolateral and the inferomedial genicular nerve. | Procedure: Diagnostic genicular nerve block<br>* Diagnostic block will be done with 1,5ml of Lidocaine 2% at the 3 target sites: the superomedial, the superolateral and the inferomedial genicular nerve.<br>Procedure: Genicular nerve block with Phenol 6%<br>* Genicular nerve block with Phenol 6% will be performed at 3 target sites: the superomedial, the superolateral and the inferomedial genicular nerve. Chemical ablation with phenol is done by injection of 1 ,5ml of phenol 6 % at the 3 target sites after infiltration with contrast dye to rule out intravascular injection. Because infiltration with phenol is painless, prior infiltration of the target site with al local anaesthetic is not necessary.<br>|
| Active Comparator: Radiofrequency ablation (RFA) of the genicular nerves<br>In our study we will make two RFA lesions at every target with 80°C for 90 seconds with a 5mm active tip. So we will make 6 lesions in total. The targets are the superomedial, the superolateral and the inferomedial genicular nerve. | Procedure: Diagnostic genicular nerve block<br>* Diagnostic block will be done with 1,5ml of Lidocaine 2% at the 3 target sites: the superomedial, the superolateral and the inferomedial genicular nerve.<br>Procedure: Genicular nerve block with Radiofrequency Ablation (RFA)<br>* Genicular nerve block with RFA will be performed at 3 target sites: the superomedial, the superolateral and the inferomedial genicular nerve. Radiofrequency ablation (RFA) is performed by creating two RFA lesions at the 3 treatment sites (6 lesions in total) after local anesthesia with 1,5ml lidocaine 2%. The lesions are made by heating the 5mm active tip of the needle to 80°C for 90 seconds.<br>|
| No Intervention: Conservative treatment<br>Examples of allowed conservative treatments during the study are patient education, physical therapy, weight loss and different pharmacological treatments. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Knee function measured with the Oxford Knee score (OKS) | Questionnaire with 12 items. Scores can range from 0 to 48, with 48 being the best outcome and a lower score indicates more functional limitations and pain. | During intake, before the intervention or study start in conservative group (T=0) and during the follow up visits (T=1 at 6weeks, T=2 at 3 months, T=3 at 6 months and T=4 at 12 months after the intervention or study start). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Osteoartritis (OA) measured by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) | We will use the WOMAC in the Likert version where question are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. So the sum of the scores ranges from 0 (the best) to 96 (the worse). | Before the intervention or study start in conservative group (T=0) and during the follow up visits (T=1 at 6weeks, T=2 at 3 months, T=3 at 6 months and T=4 at 12 months after the intervention or study start). | 
| Pain measured with the Numeric Rating Score (NRS) | NRS will be measured in rest and during the performance based tests. | In rest during intake and in rest and during performance based tests before and after the diagnostic nerve block (if applicable), before the intervention (if applicable), 6 weeks, 3 months, 6 months and 1 year after the intervention | 
| 30 seconds chair-stand test | During this test the total number of complete chair stands (up and down represents one stand) is counted. If at least a full stand is completed at 30 seconds this is counted in the total. If a person cannot stand even once then the score for the test is zero. | Before and after the diagnostic block, before the intervention (T=0), and at 6 weeks, 3 months, 6 months and 12 months follow up. In the conservative treatment group this will only be done at the applicable follow up dates. | 
| 40 meters (4x10m) fast-paced walk test | The total time taken to walk the 4 × 10 m, excluding turns, of one trial is recorded and expressed as speed m/s by dividing distance (40 m) by time (seconds). Timing is paused during turns. | Before and after the diagnostic block, before the intervention (T=0), and at 6 weeks, 3 months, 6 months and 12 months follow up. In the conservative treatment group this will only be done at the applicable follow up dates. | 
| 9-steps stair-climb test | Total time to ascend and descend steps for one trial is recorded in seconds. | Before and after the diagnostic block, before the intervention (T=0), and at 6 weeks, 3 months, 6 months and 12 months follow up. In the conservative treatment group this will only be done at the applicable follow up dates. | 
| Health related quality of life with the EQ-5D-5L | The EQ-5D descriptive system comprises the following five dimensions, each describing a different aspect of health: MOBILITY, SELF-CARE, USUAL ACTIVITIES, PAIN / DISCOMFORT and ANXIETY / DEPRESSION. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The respondent is asked to indicate his / her health state by checking the box against the most appropriate statement in each of the five dimensions. EQ-5D comprises a short questionnaire that is cognitively undemanding, taking only a few minutes to complete. | Before the intervention or study start in conservative group (T=0) and during the follow up visits (T=1 at 6weeks, T=2 at 3 months, T=3 at 6 months and T=4 at 12 months after the intervention or study start). | 
| Hospital Anxiety and Depression Scale (HADS) | The Dutch version of the HADS is a fourteen-item scale with seven items for anxiety (HADS-A) and seven items for depression (HADS-D) (49). Scoring for each item ranges from zero to three. A higher score indicates more anxiety or depression. | At T=0 (before intervention) and during T=3 (6 months after intervention) | 
| Pain Catastrophizing Score (PCS) | The Pain Catastrophizing Scale (PCS) is a 13-item self-report questionnaire considered to be the most frequent and extensively studied tool to assess pain catastrophizing for chronic pain. Patients are asked to rate the degree to which they have any of the thoughts described in the questionnaire using a 5-point Likert scale ranging from 0 (never) to 4 (always). The total score is the sum of the scores for the individual items, and ranges from 0 to 52. Higher scores indicate a higher level of catastrophizing. | At T=0 (before intervention) and during T=3 (6 months after intervention) | 
| Diagnostic block most appropriate cut-off value | The continuous results of the diagnostic nerve block in our study (percentage of pain relief) will be used to determine the best cut-off value for the positive outcome of the ablation. The cut-off value will be analysed with a receiver operating curve (ROC) analysis. Results equal or above this cut-off value are considered to predict a positive outcome of the ablation of the nerves, results below the cut-off value are considered to predict a negative outcome of the ablation of the nerve. For this analysis, a positive outcome of the ablation is defined as a MCID in OKS of 4.9 points at 3 months follow up. | Before and after the diagnostic block and during T=2 (3 months after intervention). | 
| Patient satisfaction | The patient satisfaction with the result of treatment will be measured with a 5-point Likert scale (1-5). The patients will be asked to grade the statement 'I am satisfied with the result of the treatment' with the following options: Strongly disagree Disagree Neutral Agree Strongly agree | During the follow up visits (T=1 at 6weeks, T=2 at 3 months, T=3 at 6 months and T=4 at 12 months after the intervention or study start). | 
| Patient Global Impression of Change (PGIC) | The PGIC in pain and function will be measured with a 5-point Likert scale (1-5) on the applicable follow up visits. The patients will be asked to rate the following statements: Please imagine how you would have described your pain intensity before the procedure. How do you feel today as compared to baseline (Start of the study) as far as your knee pain caused by OA is concerned? Please imagine how you would have described the functionality of your knee before the procedure. How do you feel today as compared to baseline (start of the study) as far as your knee functionality caused by OA is concerned? The options on the Likert scale are: much better slightly better no change slightly worse much worse | During the follow up visits (T=1 at 6weeks, T=2 at 3 months, T=3 at 6 months and T=4 at 12 months after the intervention or study start). | 
| Minimal Clinically Important Difference (MCID) of the OKS | We will use distribution and anchor based methods to determine the MCID on the patient reported outcomes of the OKS. | MCIDs will be determined for our population on T=1 (6weeks), T=2 (3 months) and T=3 (6 months) follow up. . | 
| Minimal Clinically Important Difference (MCID) of the WOMAC | We will use distribution and anchor based methods to determine the MCID on the patient reported outcomes of the WOMAC. | MCIDs will be determined for our population on T=1 (6weeks), T=2 (3 months) and T=3 (6 months) follow up. | 
| Minimal Clinically Important Difference (MCID) for the EQ-5D-5L | To determine the MCID on the patient reported outcomes of the EQ-5D-5L we will use an instrument defined method. | MCIDs will be determined for our population on T=1 (6weeks), T=2 (3 months) and T=3 (6 months) follow up. | 
| Minimal Clinically Important Difference (MCID) of the 30 seconds chair-stand test | We will use distribution and anchor based methods to determine the MCID of the 30 seconds chair-stand test. | MCIDs will be determined for our population on T=1 (6weeks), T=2 (3 months) and T=3 (6 months) follow up. | 
| Minimal Clinically Important Difference (MCID) of the 40 meters (4x10m) fast-paced walk test | We will use distribution and anchor based methods to determine the MCID of the 40 meters (4x10m) fast-paced walk test. | MCIDs will be determined for our population on T=1 (6weeks), T=2 (3 months) and T=3 (6 months) follow up. | 
| Minimal Clinically Important Difference (MCID) of the 9-steps stair-climb test. | We will use distribution and anchor based methods to determine the MCID of the 9-steps stair-climb test. | MCIDs will be determined for our population on T=1 (6weeks), T=2 (3 months) and T=3 (6 months) follow up. | 
| Adverse events | The reported treatment related or probably treatment related adverse events will be listed as numbers with frequencies per treatment. | After the diagnostic block, after the intervention (T=0), and at 6 weeks, 3 months, 6 months and 12 months follow up. | 
| Medication changes | The patients will be asked to report changes in the use of NSAIDs and opioids during the follow up visits. The results will be summarised as increased use, no change, decrease in use and use of opioids will be reported as MME. | Before the intervention (T=0), and at 6 weeks, 3 months, 6 months and 12 months follow up. | 
| Number of Total Knee Artroplasty's (TKA's) | The number of TKAs during the study follow up will be documented including the point in time since the intervention. If applicable, we will use the Kaplan-Meier estimator to estimate the survival function. | At 6 weeks, 3 months, 6 months and 12 months follow up. | 
| Procedure time | The total procedure time of chemical ablation and RFA will be measured in minutes. The measurement starts as soon as the treating physician puts on his sterile gloves and will end when the sterile draping is taken off. | During the intervention visit (T=0) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Thermal ablation, Phenol neurolysis, Genicular nerve