Cocogen Trial: COoled Versus COnventional Radiofrequency Treatment of the GENicular Nerves for Chronic Knee Pain

Study Overview
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Brief Summary
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Knee osteoarthritis is a progressive degenerative process that affects joint cartilage and the subchondral bone. Approximately 10% to 30% of all osteoarthritis patients suffer from disabling symptoms such as pain, stiffness and loss of function leading to psychological and sleeping disorders and a diminished quality of life. When conservative treatment fails to treat the symptoms, a total knee arthroplasty can be performed. However, this procedure is not suitable for all patients. For these specific groups of patients a radiofrequent treatment of the genicular nerves might be an alternative treatment option. Multiple researchers investigated the effect of conventional and later also, cooled radiofrequent treatment of the genicular nerves, with promising results for both techniques. However, the techniques have never been compared in a randomised controlled trial. This study is designed to assess the feasibility of conducting a large RCT comparing pain relief and costs after a conventional radiofrequency treatment of the genicular nerves (superomedial, superolateral and inferomedial) versus a cooled radiofrequency treatment.

Detailed Description
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This pilot study is designed as a prospective, multicentre, double blind, randomised controlled non-inferiority trial. The total follow up time is 6 months with follow up assessments at 1, 3 and 6 months post intervention. It is estimated that the total duration of data collection will cover 1 year. Adult patients (> 18 years) with chronic, moderate to severe knee pain (NRS>4) due to osteoarthritis, radiological diagnosed to be graded 2-4 according to the Kellgren-Lawrence criteria or with persistent postoperative moderate to severe knee pain (NRS>4) after total knee arthroplasty can be included in the study. Patients will be randomly selected for treatment with conventional radiofrequent treatment or cooled radiofrequent treatment of the SL, SM and IL genicular nerves. In total, three hospitals participate in this study: Ziekenhuis Oost-Limburg (Belgium), Maastricht UMC+ (Netherlands) and Rijnstate (Netherlands).

Official Title
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Comparison of Cooled Versus Conventional Radiofrequency Treatment of the Genicular Nerves for Chronic Knee Pain: a Multicentre Randomised Controlled Non-inferiority Pilot Trial

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Device: Cooled radiofrequent treatment
* Device: Conventional radiofrequent treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Able to understand the informed consent form and provide written informed consent and able to complete outcome measures. Chronic anterior knee pain (> 12 months) with an NRS > 4 on most or all days for the index knee either constantly or with motion. Unresponsive to conventional treatments continued during 12 months including physiotherapy, oral analgesics or intra-articular infiltrations. Radiologic confirmation of arthritis of OA grade of 2 (mild), 3 (moderate) or 4 (severe) noted within 6 months for the index knee according the Kellgren Lawrence criteria (27) diagnosed by an independent radiologist with experience in musculoskeletal imaging or patients with total knee arthroplasty of the index knee with a negative orthopaedic workout. Other therapies (including surgical interventions) for pain in the index knee are allowed for the period of the study follow up as long as they are documented. This is necessary to correctly estimate the costs in the cost effectiveness analyses. Allowing patients to receive additional treatments will also improve the protocol compliance. Agree to provide informed consent and to comply with the requirements of this protocol for the full duration of the study Exclusion Criteria: Patient refusal to comply to protocol procedures or schedule Local or systemic infection (bacteraemia) Evidence of inflammatory arthritis or an inflammatory systemic disease responsible for knee pain Intra-articular injections (steroids, hyaluronic acid, platelet enriched plasma, …) in the index knee during the 3 months prior to procedure Body mass index (BMI) > 40 kg/m2 Pregnant, nursing or planning to become pregnant Chronic widespread pain before the treatment Patients with psychosocial dysfunction will be referred for further psychological follow up prior to possible inclusion Allergies to products used during the procedure Uncontrolled coagulopathy defined as supratherapeutic dose of anticoagulation medication. Uncontrolled immune suppression Participating in another clinical trial/investigation within 30 days prior to signing informed consent Patient is currently implanted with a defibrillator, neuromodulator or other electrical devices Radicular pain in index leg Patient received previous conventional or cooled radiofrequency of the index knee

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Prospective, multicentre, double blind, randomised controlled, non-inferiority, pilot study.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional radiofrequent treatment<br>The patient is placed in a supine position on a fluoroscopy table with the index knee flexed 10-15°. The procedure is performed with a 100 mm long, 18 G straight RF cannula/introducer (Halyard) with a probe/electrode with a 10 mm active tip | Device: Conventional radiofrequent treatment<br>* In the conventional radiofrequency group a treatment of 80°C at the tip is applied during 90 seconds at each nerve.<br>|
| Active Comparator: Cooled radiofrequent treatment<br>The procedure is performed with a 100 mm long, 18 G straight RF cannula/introducer (Halyard) with a probe/electrode with a 100 mm long, 17 G RF cannula/introducer with an 18 G cooled probe/electrode with a 4 mm active tip (Halyard/Coolief). | Device: Cooled radiofrequent treatment<br>* In the cooled radiofrequency group a treatment of 60°C measured at the tip and on average 80°C in the targeted tissue is applied during 150 seconds using the Coolief system.<br>* Other names: COOLIEF™ system;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in pain intensity | NRS is a unidimensional, subjective measurement of pain intensity, expressed by the patient as a number between 0 and 10. It is a 11 point scale in which 0 equals no pain and 10 maximal pain. | at 1, 3, 6 and 12 months post intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient self-reported impression of change | Patient self-reported impression of change, measured by the Patient's Global Impression of Change (PGIC). The impression of change is measured using a 7 point likert scale ranging from very much worse (7) to very much improved (1). | at 1, 3, 6 and 12 months post intervention | 
| The change in medication use | The change in medication use, measured by the change in Medication Quantification Scale III (MQS III). The MQS is designed as a methodology of quantifying different drug regimens in 1992 and updated in 1998 (MQS II) and 2003 (MQS III) using detriment weights determined by surveying physician members of the American Pain Society | at 1, 3, 6 and 12 months post intervention | 
| The duration of pain relief | This is defined as the time interval in which a NRS reduction of more than 50% is obtained or in which the pain is still acceptable without the usage of other additional therapies (increase in MQS 3 score of more than 50%, intra-articular infiltration, operation) | at 3, 6 and 12 months post intervention | 
| The change in physical function | This will be measured by the change in the Oxford Knee Score (OKS). The OKS is a patient-reported measure assessing pain intensity and physical function. The list consists of 12 items scored from 1 to 5, with 0 representing normal function/ least symptoms. | at baseline, 3, 6 and 12 months post intervention | 
| The change in health-related quality of life | This measured by the change in EQ-5D-5L,intervention.The EQ-5D-5L is a patient-reported generic measure of HRQoL comprising five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Responses to the 5 items (one for each dimension) result in a patient's health state that can be transformed into a utility score ranging between 0 (death) and 1 (full health), representing the quality of life of the health state. | at baseline and at 1, 3, 6 and 12 months post intervention. | 
| Hospital Anxiety and Depression Scale (HADS) | HADS is developed to detect anxiety and depression in patients with physical health problems. The questionnaire consists of 14 items: 7 items to measure anxiety and 7 items to measure depression | at baseline and at 1, 3, 6 and 12 months post intervention. | 
| Pain Catastrophizing Scale (PCS) | The PCS is often used in clinical settings to measure catastrophic thinking related to pain. The 13 item questionnaire consists of 3 subscales (magnification, rumination and helplessness) and asks patients to reflect on past painful experiences and to indicate the degree on which they experiences each of 13 thoughts of feelings on a 5- point scale (0 not at all and 4 all the time). | at baseline and at 1, 3 and 6 months post intervention. | 
| Goniometry knee | Knee flexion and extension is assessed using a phone app meant to simulate a goniometer. The goniometry results are expressed in degrees. | at baseline and at 3 and 6 months post intervention. | 
| Timed up and go test | In the timed up and go test, subjects are asked to rise from a standard armchair, walk to a marker 3 m away, turn, walk back, and sit down again. The results are expressed in minutes or seconds. | at baseline and at 3 and 6 months post intervention. |