Knee OsteoarthritisNCT03865849
Cocogen Trial: COoled Versus COnventional Radiofrequency Treatment of the GENicular Nerves for Chronic Knee Pain
A study testing Cooled radiofrequent treatment and Conventional radiofrequent treatment in people with Knee Osteoarthritis, run by Ziekenhuis Oost-Limburg at 3 sites in 2 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Knee Osteoarthritis
- What is being tested?
- Cooled radiofrequent treatment and Conventional radiofrequent treatment
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 2 Feb 2020to 28 Oct 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Netherlands2 sites
Pain Medicine Rijnstate
Arnhem
Pain Medicine, Maastricht University Medical Centre
Maastricht
About this study
Official title: Comparison of Cooled Versus Conventional Radiofrequency Treatment of the Genicular Nerves for Chronic Knee Pain: a Multicentre Randomised Controlled Non-inferiority Pilot Trial
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.
Read the detailed description
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).
- Conditions
- Knee Osteoarthritis
- Being tested
- Cooled radiofrequent treatment, Conventional radiofrequent treatment
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cooled radiofrequent treatmentDevice
Also called COOLIEF™ system
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.
Conventional radiofrequent treatmentDevice
In the conventional radiofrequency group a treatment of 80°C at the tip is applied during 90 seconds at each nerve.
| Study group | Role | What they receive |
|---|---|---|
| Conventional radiofrequent treatment | Active comparator | 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 Receives: Device: Conventional radiofrequent treatment |
| Cooled radiofrequent treatment | Active comparator | 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). Receives: Device: Cooled radiofrequent treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: at 1, 3, 6 and 12 months post intervention
Secondary outcomes (9)
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)."
Measured: 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
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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).
Measured: 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.
Measured: 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.
Measured: at baseline and at 3 and 6 months post intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2019
- Study start2 Feb 2020
- Primary completion28 Jul 2021
- Study completion28 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Knee OsteoarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, multicentre, double blind, randomised controlled, non-inferiority, pilot study.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ziekenhuis Oost-Limburg
- Sponsor type
- University, hospital or other
- Collaborators
- Rijnstate Hospital, Maastricht University Medical Center
- Responsible party
- Principal investigator, Jan Van Zundert, Ziekenhuis Oost-Limburg
- Investigators
- Jan Van Zundert, MD, Principal investigator, Maastricht University Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03865849
- Sponsor's protocol ID
- COCOGEN
- Status last verified
- Apr 2023
- First submitted
- 4 Mar 2019
- Last updated
- 13 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Belba A, Vanneste T, Kallewaard JW, van Kuijk SM, Gelissen M, Emans P, Bellemans J, Smeets K, Van Boxem K, Sommer M, Kimman M, Van Zundert J. Cooled versus conventional radiofrequency treatment of the genicular nerves for chronic knee pain: 12-month and cost-effectiveness results from the multicenter COCOGEN trial. Reg Anesth Pain Med. 2025 Jan 7;50(1):36-45. doi: 10.1136/rapm-2023-105127.
PubMed 38388017Vanneste T, Belba A, Kallewaard JW, van Kuijk SMJ, Gelissen M, Emans P, Bellemans J, Smeets K, Terwiel C, Van Boxem K, Sommer M, Van Zundert J. Comparison of cooled versus conventional radiofrequency treatment of the genicular nerves for chronic knee pain: a multicenter non-inferiority randomized pilot trial (COCOGEN trial). Reg Anesth Pain Med. 2023 May;48(5):197-204. doi: 10.1136/rapm-2022-104054. Epub 2023 Jan 18.
PubMed 36653065
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Cooled Versus Conventional Radiofrequency Treatment of the Genicular Nerves for Chronic Knee Pain: a Multicentre Randomised Controlled Non-inferiority Pilot Trial
- ClinicalTrials.gov ID
- NCT03865849
- Acronym / sponsor ID
- COCOGEN
- Conditions
- Knee Osteoarthritis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Ziekenhuis Oost-LimburgUniversity, hospital or other
- Collaborators
- Rijnstate Hospital, Maastricht University Medical Center
- Study start
- 2 Feb 2020 (actual)
- Primary completion
- 28 Jul 2021 (actual)
- Study completion
- 28 Oct 2021 (actual)
- First posted
- 7 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Prospective, multicentre, double blind, randomised controlled, non-inferiority, pilot study.
| Arm | Type | Receives |
|---|---|---|
| Conventional radiofrequent treatment | Active comparator | Device: Conventional radiofrequent treatmentThe 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 |
| Cooled radiofrequent treatment | Active comparator | Device: Cooled radiofrequent treatmentThe 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cooled radiofrequent treatmentAlso: COOLIEF™ systemIn 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. | Device | Cooled radiofrequent treatment |
| Conventional radiofrequent treatmentIn the conventional radiofrequency group a treatment of 80°C at the tip is applied during 90 seconds at each nerve. | Device | Conventional radiofrequent treatment |
Primary outcome
The change in pain intensity
Time frame: at 1, 3, 6 and 12 months post intervention
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.
9 secondary outcomes
Patient self-reported impression of change
Time frame: at 1, 3, 6 and 12 months post intervention
The change in medication use
Time frame: at 1, 3, 6 and 12 months post intervention
The duration of pain relief
Time frame: at 3, 6 and 12 months post intervention
The change in physical function
Time frame: at baseline, 3, 6 and 12 months post intervention
The change in health-related quality of life
Time frame: at baseline and at 1, 3, 6 and 12 months post intervention.
Hospital Anxiety and Depression Scale (HADS)
Time frame: at baseline and at 1, 3, 6 and 12 months post intervention.
Pain Catastrophizing Scale (PCS)
Time frame: at baseline and at 1, 3 and 6 months post intervention.
Goniometry knee
Time frame: at baseline and at 3 and 6 months post intervention.
Timed up and go test
Time frame: at baseline and at 3 and 6 months post intervention.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2023.
- Derived from this study: PubMed 38388017Belba A, Vanneste T, Kallewaard JW, van Kuijk SM, Gelissen M, Emans P, Bellemans J, Smeets K, Van Boxem K, Sommer M, Kimman M, Van Zundert J. Cooled versus conventional radiofrequency treatment of the genicular nerves for chronic knee pain: 12-month and cost-effectiveness results from the multicenter COCOGEN trial. Reg Anesth Pain Med. 2025 Jan 7;50(1):36-45. doi: 10.1136/rapm-2023-105127.
- Derived from this study: PubMed 36653065Vanneste T, Belba A, Kallewaard JW, van Kuijk SMJ, Gelissen M, Emans P, Bellemans J, Smeets K, Terwiel C, Van Boxem K, Sommer M, Van Zundert J. Comparison of cooled versus conventional radiofrequency treatment of the genicular nerves for chronic knee pain: a multicenter non-inferiority randomized pilot trial (COCOGEN trial). Reg Anesth Pain Med. 2023 May;48(5):197-204. doi: 10.1136/rapm-2022-104054. Epub 2023 Jan 18.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jan Van Zundert, MD principal investigator
Maastricht University Medical Centre
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cooled radiofrequent treatment and Conventional radiofrequent treatment in people with Knee Osteoarthritis, run by Ziekenhuis Oost-Limburg at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The change in pain intensity (time frame: at 1, 3, 6 and 12 months post intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03865849, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2023.