Clinical trial NCT05407610: Comparison of Conventional and Cooled Radiofrequency of the Genicular Nerves in Patients With Chronic Knee Pain
Official title: Comparison of Conventional and Cooled Radiofrequency Treatment of the Genicular Nerves Versus Sham Procedure for Patients With Chronic Knee Pain: a Multicentre, Double Blind, Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Knee Osteoarthritis
Persistent Postsurgical Pain
Chronic Knee Pain
Keywords: Osteoarthritis
Persistent Postsurgical Pain
Knee
Radiofrequency ablation
Lead sponsor: Ziekenhuis Oost-Limburg
Sponsor class: OTHER
Collaborators: name: Belgium Health Care Knowledge Centre
name: Klinische Epidemiologie en Medical Technology Assessment
First posted: 2022-06-07
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Three-arm, pragmatic, prospective, multicentre, double blind, randomised sham-controlled trial
Primary purpose: TREATMENT

Brief summary: Chronic knee pain remains a disabling disease despite current treatment strategies. There is an increase in the prevalence of osteoarthritis (OA) of the knee in the general population, presently affecting approximately 450,000 individuals in Belgium. A total knee replacement is a viable alternative for severe knee OA that does not respond to conservative therapy. Unfortunately, up to 53% of patients who undergo a total knee replacement develop persistent post-surgical pain (PPSP). There is currently no effective therapy for PPSP.

A radiofrequency (RF) treatment applies high frequency current on the nerve responsible for pain conduction, resulting in an interruption of the transmission of pain. This can be applied to the nerves innervating the knee joint - the superolateral, superomedial and inferomedial genicular nerves - and could be an alternative, minimally invasive treatment for patients with knee OA who fail conservative treatments and for patients with PPSP. Data from the recent literature indicates that this treatment leads to a reduction of pain intensity and could result in an improvement of knee function, of the psychological state of the individual, and finally in an increase in health-related quality of life. Furthermore, RF of the genicular nerves could help avoid or delay a total knee replacement therefore potentially contributing to cost reduction. Both cooled and conventional RF treatments are reported in the literature to improve pain. The use of water to cool the RF electrodes results in an increased lesion size by removing heat from adjacent tissue, allowing power delivery to be increased. As a consequence, cooled RF could result in a higher chance of success and longer duration of effect. Until now, the studies performed on cooled RF are industry initiated and a direct comparison between conventional, cooled and a sham procedure is lacking.

The aim of the COGENIUS trial is to investigate the effect of the two types of RF treatment on individuals experiencing chronic knee pain that is resistant to conservative treatments. For this purpose, the efficacy and cost-effectiveness of cooled and conventional RF will be compared to a sham procedure in patients suffering from knee OA and PPSP after total knee replacement.

Detailed description: In this three-arm, pragmatic, prospective, multicentre, double blind, randomised sham-controlled trial of approximately 4 years duration, 400 patients with chronic moderate to severe anterior knee pain (\>12 months) refractory to conventional treatments will be included. Two groups of chronic knee pain patients will be enrolled depending on the aetiology of knee pain: OA and PPSP. Each patient will undergo a run-in period of 1 to 3 months depending on the previous treatments of the patient. A run-in period is added to the trial to guarantee that conservative treatment is performed in an optimal way before randomisation. In each group (osteoarthritis and persistent post-surgical pain), non-responders to the run-in period will be randomly allocated to a conventional RF intervention of the genicular nerves, a cooled RF intervention of the genicular nerves or a sham procedure in a 2:2:1 ratio. The patients will be followed up for a period of 2 years.

Eligibility criteria: Inclusion Criteria:

* Signed written informed consent must be obtained before any study assessment is performed.
* Adult patients (Age ≥ 18 years old).
* Chronic anterior knee pain (\> 12 months) that is moderate to severe (defined as NRS \> 4 on most or all days for the index knee either constantly or with motion at time of screening and, an average NRS score reported in the patient diary \>4 at the end of the run-in period).
* Unresponsive (meaning insufficient pain reduction or intolerance) to conventional treatments ongoing for at least 12 months prior to inclusion. Conventional treatments must include all of the following: active physiotherapy, pharmacological treatment of pain and intra-articular corticosteroid infiltration.
* Only for patients with Osteoarthritis (OA): Radiologic confirmation of knee osteoarthritis of grade 2 (mild), 3 (moderate) or 4 (severe) noted within 12 months prior to the screening for the index knee according the Kellgren Lawrence criteria diagnosed by an independent radiologist with experience in musculoskeletal imaging on radiography (Rx) or magnetic resonance imaging (MRI). If imaging will need to be performed at screening it is recommended to perform an MRI instead of Rx. Imaging with MRI will enable the independent radiologist to perform a better estimation of the grade of OA.
* Only for patients with Persistent Post-Surgical Pain (PPSP) after Total Knee Arthroplasty (TKA): Patients with PPSP\* after TKA need to have had a negative orthopaedic work-up

Exclusion Criteria:

* 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.
* Pregnant, nursing or planning to become pregnant before the study intervention. Participants who become pregnant after the study intervention during the follow-up period will not be excluded.
* Chronic widespread pain.
* Patients with unstable psychosocial disorder.
* Allergies to products used during the procedure (lidocaine, propofol, chlorhexidine).
* 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 neurostimulator.
* Current radicular pain in index leg.
* Previous conventional or cooled radiofrequency of the index knee.
* Patients with bilateral knee pain defined as chronic knee pain (\> 12 months) in both knees that is moderate to severe (defined as a numeric rating scale (NRS) \> 4 on most or all days either constantly or with motion) and that is unresponsive (meaning insufficient pain reduction or intolerance) to conventional treatments ongoing for at least 12 months prior to inclusion. Conventional treatments must include all of the following: active physiotherapy, pharmacological treatment of pain and intra-articular corticosteroid infiltration.
* 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 who are unwilling or mentally incapable to complete the study questionnaires.

Primary outcomes:
measure: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 6 months post-intervention
timeFrame: 6 months post-intervention.
Secondary outcomes:
measure: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score.
timeFrame: 1-, 3-, 6-, 12- and 24-months post-intervention.
measure: Pain Intentisty
timeFrame: 1-, 3-, 6-, 12- and 24-months post-intervention.
measure: The proportion of patients with a pain reduction of at least 50% compared to baseline expressed by the numerical rating scale (NRS)
timeFrame: 1-, 3-, 6-, 12- and 24-months post-intervention.
measure: Health-related quality of life
timeFrame: 1-, 3-, 6-, 9-, 12- and 24-months post-intervention.
measure: Goniometry
timeFrame: 1-, 3-, 6-, 12- and 24-months post-intervention.
measure: 'Timed up and Go' test
timeFrame: 1-, 3-, 6-, 12- and 24-months post-intervention.
measure: The 6-minute walk test
timeFrame: 1-, 3-, 6-, 12- and 24-months post-intervention.
measure: The Hospital Anxiety and Depression Scale (HADS)
timeFrame: 1-, 3-, 6-, 12- and 24-months post- intervention.
measure: The Pain Catastrophizing Scale (PCS)
timeFrame: 1-, 3-, 6-, 12- and 24-months post- intervention.
measure: Patient Global Impression of Change (PGIC)
timeFrame: 1-, 3-, 6-, 12- and 24-months post- intervention.
measure: Patient's satisfaction
timeFrame: 1-, 3-, 6-, 12- and 24-months post- intervention.
measure: Medication use
timeFrame: 1-, 3-, 6-, 9-, 12- and 24-months post- intervention.
measure: Opioid dependence
timeFrame: 1-, 3-, 6-, 9-, 12- and 24-months post- intervention.
measure: Incidence of related adverse events
timeFrame: Follow-up until 24-months post- intervention.
measure: Health care resource utilisation
timeFrame: Follow-up until 24-months post- intervention.
measure: Productivity loss due to sickness
timeFrame: Follow-up until 24-months post- intervention.
Other outcomes:
measure: Phenotype of patients suffering from Persistent Post-Surgical Pain (PPSP)
timeFrame: Baseline
measure: Time to additional interventions
timeFrame: Follow-up until 24-months post- intervention.
Locations:
city: Antwerpen
country: Belgium
facility: UZ Antwerpen
city: Brasschaat
country: Belgium
facility: AZ Klina
city: Brussel
country: Belgium
facility: ULB Erasme
city: Brussel
country: Belgium
facility: UCL Saint-Luc
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg AV
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: CHR de la Citadelle
city: Liège
country: Belgium
facility: CHU Liège
city: Roeselare
country: Belgium
facility: AZ Delta
city: Turnhout
country: Belgium
facility: AZ Turnhout
city: Arnhem
country: Netherlands
facility: Rijnstate
city: Maastricht
country: Netherlands
facility: MUMC
Study officials:
References: