Comparison of Conventional and Cooled Radiofrequency of the Genicular Nerves in Patients With Chronic Knee Pain

NCT ID: NCT05407610

Last Updated: 2023-05-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-07
• Study Completion Date: 2026-09-01

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.

Conditions

Knee Osteoarthritis; Persistent Postsurgical Pain; Chronic Knee Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Conventional Radiofrequency of the genicular nerves

In the conventional radiofrequency group a intervention of 80°C at the tip is applied during 90 seconds at each nerve (superolateral, superomedial and inferomedial genicular nerves). The probe stays in place for 150 seconds at each nerve so that the time needed for each procedure is similar.

Group Type: ACTIVE_COMPARATOR

Conventional Radiofrequency ablation of the genicular nerves

Intervention Type: PROCEDURE

Conventional Radiofrequency treatment of the genicular nerves of the knee blocks the transmission of painful stimuli from the sensory genicular nerves of the knee to the central nervous system by means of a thermal lesion created using RF current.

Cooled Radiofrequency of the genicular nerves

In the cooled radiofrequency group a intervention of 60°C measured at the tip and on average 80°C in the targeted tissue is applied for 150 seconds using the Cooled RF system at each nerve (superolateral, superomedial and inferomedial genicular nerves).

Group Type: ACTIVE_COMPARATOR

Cooled Radiofrequency ablation of the genicular nerves

Intervention Type: PROCEDURE

Cooled RF treatment causes a larger lesion size compared to conventional RF by means of internal cooling of the probe.

Sham procedure

In the sham group a 18 gauge introducer and probe will be placed but no RF intervention will be applied. The generator will be turned on without connection to the probe for 150 seconds and the sound of the generator will be mimicked with a recording. The position of the needle will not be checked by fluoroscopy; however, the intervention team will position the fluoroscopy arm and mention the acquisition of the fluoroscopic image to the patient. This way no unnecessary radiation is used.

Group Type: SHAM_COMPARATOR

Sham procedure

Intervention Type: PROCEDURE

Sham procedure with placing of needles subcutaneously.

Interventions

Conventional Radiofrequency ablation of the genicular nerves

Conventional Radiofrequency treatment of the genicular nerves of the knee blocks the transmission of painful stimuli from the sensory genicular nerves of the knee to the central nervous system by means of a thermal lesion created using RF current.

Intervention Type: PROCEDURE

Cooled Radiofrequency ablation of the genicular nerves

Cooled RF treatment causes a larger lesion size compared to conventional RF by means of internal cooling of the probe.

Intervention Type: PROCEDURE

Sham procedure

Sham procedure with placing of needles subcutaneously.

Intervention Type: PROCEDURE

Other Intervention Names

Conventional Radiofrequency ablation; Cooled Radiofrequency ablation

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Belgium Health Care Knowledge Centre

OTHER_GOV

Sponsor Role: collaborator

Klinische Epidemiologie en Medical Technology Assessment

UNKNOWN

Sponsor Role: collaborator

Ziekenhuis Oost-Limburg

OTHER

Sponsor Role: lead

Responsible Party

Jan Van Zundert

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

UZ Antwerpen

Antwerp, , Belgium

Site Status: RECRUITING

AZ Klina

Brasschaat, , Belgium

Site Status: ACTIVE_NOT_RECRUITING

ULB Erasme

Brussels, , Belgium

Site Status: RECRUITING

UCL Saint-Luc

Brussels, , Belgium

Site Status: ACTIVE_NOT_RECRUITING

Ziekenhuis Oost-Limburg AV

Genk, , Belgium

Site Status: RECRUITING

AZ Maria Middelares

Ghent, , Belgium

Site Status: RECRUITING

Jessa Ziekenhuis

Hasselt, , Belgium

Site Status: RECRUITING

AZ Groeninge

Kortrijk, , Belgium

Site Status: ACTIVE_NOT_RECRUITING

UZ Leuven

Leuven, , Belgium

Site Status: RECRUITING

CHR de la Citadelle

Liège, , Belgium

Site Status: RECRUITING

CHU Liège

Liège, , Belgium

Site Status: ACTIVE_NOT_RECRUITING

AZ Delta

Roeselare, , Belgium

Site Status: RECRUITING

AZ Turnhout

Turnhout, , Belgium

Site Status: RECRUITING

Rijnstate

Arnhem, , Netherlands

Site Status: ACTIVE_NOT_RECRUITING

MUMC

Maastricht, , Netherlands

Site Status: RECRUITING

Countries

Belgium; Netherlands

Central Contacts

Jan Van Zundert

Role: CONTACT

cogenius@zol.be

+32 (0)89 32.52.54

Charlotte Claes

Role: CONTACT

cogenius@zol.be

+32 (0)89 21.20.85

References

Vanneste T, Belba A, van Kuijk S, Kimman M, Bellemans J, Bonhomme V, Sommer M, Emans P, Vankrunkelsven P, Tartaglia K, Van Zundert J. Comparison of conventional and cooled radiofrequency treatment of the genicular nerves versus sham procedure for patients with chronic knee pain: protocol for a multicentre, double-blind, randomised controlled trial (COGENIUS). BMJ Open. 2023 Aug 2;13(8):e073949. doi: 10.1136/bmjopen-2023-073949.

Reference Type: DERIVED

PMID: 37532482 (View on PubMed)

Other Identifiers

Z-2021109

Identifier Type: OTHER

Identifier Source: secondary_id

KCE20-1255

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

COGENIUS

Identifier Type: -

Identifier Source: org_study_id