Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001157763
Ethics application status
Approved
Date submitted
1/07/2021
Date registered
24/08/2022
Date last updated
24/08/2022
Date data sharing statement initially provided
24/08/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Genicular artery embolisation and the effect on Knee Osteoarthritis - a randomised controlled trial.
Scientific title
Safety and Efficacy of Genicular artery embolisation and the effect on knee osteoarthritis - a randomised controlled trial.
Secondary ID [1] 304556 0
Nil known
Universal Trial Number (UTN)
Trial acronym
KOGAE trial.
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Knee osteoarthritis 322434 0
Condition category
Condition code
Musculoskeletal 320088 320088 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The research team will be studying the impact that embolisation of neo-vascularisation of the geniculate arteries has on patient’s pain and functional outcomes associated with their knee osteoarthritis.

Brief name: geniculate artery embolization, there will be two arms to this study; an intervention arm and a placebo/control arm.

The procedures will be carried out face to face by a qualified Interventional Radiologist with a minimum of 3 years’ experience of performing endovascular procedures. The procedures will be carried out at the interventional radiology department within Liverpool Hospital, NSW, Australia. The team aims to carry out one procedure for each participant with the timing of procedures ranging from 2-3hours.

Intervention description:
The contralateral/ipsilateral femoral artery or ipsilateral dorsalis pedis artery will be assessed with ultrasound. The region will be prepped utilising sterile technique.
The artery will be punctured; an endovascular sheath used to replace the needle using seldinger technique. Guide wires, angiographic catheters/microcatheters will be advanced to the affected knee and the abnormal/neovascularised vessels will be imaged with diagnostic angiography.
The abnormal arteries will then be embolised utilising micron embosphere beads.

Vessel anatomy and the abnormal/neovascularised vessels will differ from one patient to another. Thus, each participant will have personalised or adapted treatment. These personalised differences will range from
- Puncture/ arterial access site.
- Type of catheters/microcatheters used.
- Number of vessels embolised.
- Determine the number of vessels needed to be embolised due to the patient’s symptoms at the time of the original consultation.

These treatment differences will occur at the time of the intervention.

The procedure is a one time procedure, there is no need for strategies to monitor adherence/fidelity.
Intervention code [1] 320905 0
Treatment: Other
Comparator / control treatment
The intervention group will be compared with the placebo/control group.
Within this group, each participant will have the contralateral/ipsilateral femoral artery or ipsilateral dorsalis pedis artery will be assessed with ultrasound. The region will be prepped utilising sterile technique.
The artery will be punctured; an endovascular sheath used to replace the needle using seldinger technique. Guide wires, angiographic catheters/microcatheters will be advanced to the affected knee and the abnormal/neo-vascularised vessels will be imaged with diagnostic angiography.

No embolisation will be performed.

The procedures will not be directly matched (timing wise) as some patients may have more complex anatomy requiring a longer time for the procedure to be completed compared to others. The research team does have a minimum procedure duration time of 30 minutes to ensure that the comparator procedure will be of an appropriate time to resemble the actual procedure to the intervention procedure.
Control group
Placebo

Outcomes
Primary outcome [1] 327962 0
Safety of transcatheter arterial embolisation of genicular arteries in the treatment of pain from knee osteoarthritis.


Safety will be monitored at a variety of check points.
all adverse events will documented and alerted to the principle sponsor and the local HREC office.
Timepoint [1] 327962 0
Patients will be monitored at regular intervals post procedure for 12 months. These intervals include day 1 post procedure, week one post procedure, 1,3,6 and 12 months post procedure.
Primary outcome [2] 327963 0
Efficacy of transcatheter arterial embolisation of genicular arteries in the treatment of pain from knee osteoarthritis.

Treatment efficacy is assessed via a composite of the VAS and Knee injury and osteoarthritis outcome score.
Timepoint [2] 327963 0
The time points for assessment will be at
baseline, day 1, 1 week, 3 months, 6 months and 12 months (primary end point) post procedure.
Primary outcome [3] 327964 0
Assessment of pain in patients who undergo genicular artery embolisation in comparison with the control group who do not undergo the procedure.
Pain will be assessed by a composite of the Visual analogue scale, Knee injury osteoarthritis outcome score and the usage of their analgesia (reduction or increase).
Analgesia usage will be determined by review of the participants diaries.
Timepoint [3] 327964 0
Pain will be assessed at the previously mentioned time points i.e. at baseline, day 1, 1 week, 3 months, 6 months and 12 months (primary end point) post procedure
Secondary outcome [1] 397121 0
Assessment of quality of life in patients who undergo genicular artery embolisation in comparison with the control group who do not undergo the procedure.

Quality of life will be assessed via a subset of the questions in the knee injury and osteoarthritis outcome score.
Timepoint [1] 397121 0
The time points for assessment will be at
baseline, day 1, 1 week, 3 months, 6 months and 12 months post procedure.
Secondary outcome [2] 410974 0
Pedal vessel patency
Timepoint [2] 410974 0
ultrasound of the pedal arteries will be done at baseline and then one week post procedure.

Eligibility
Key inclusion criteria
>40 years of age.
Grade 2 and 3 knee Osteoarthritis on plain radiographs (Kellgren-lawrence scale).
Knee pain for 6 months or more, moderate to severe knee pain (VAS >50mm).
Pain refractory to conservative management for at least 3 months.
Patients capable of consenting for the trial.
Minimum age
41 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Current local infection.
Life expectancy is less than 6 months.
Active malignancy.
Grade 1 or 4 knee OA on x-rays as per Kellgren-Lawrence Grading scale.
Known advanced atherosclerosis in lower limb.
Rheumatoid or infectious arthritis.
Prior ipsilateral knee surgery excluding arthroscopic surgery more than three months ago.
Uncorrectable coagulopathy greater with INR greater than 1.5 (APTT will not be taken).
Renal dysfunction as defined by eGFR <45 within the last 60 days.
Contraindications for MR imaging.
Known history of allergy to contrast media.
Women who are lactating, pregnant or trying to become pregnant.
Patients with a history of psychological illness, especially severe depression.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The allocation was concealed by utilising a computer based randomisation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Dynamic random allocation method (minimisation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
54 patients (27 in each arm) in total are needed for statistical significance. This is based on previous research which states that the mean Knee Injury and Osteoarthritis Severity Score (KOOS) ranges from 48-57, assuming an average of 50 with a standard deviation of 13 and assuming a 20% reduction in the KOOS score will be significant. Thus a total of 54 patients (27 in each group is needed).

After compiling all study questionnaires, the overall assessment between the two groups will be carried out using two sample T tests to assess the difference between intervention and placebo group. In addition, the use of means, medians and averages will also allow understanding of the cohort demographics (age, KOOS score etc). The above statistics was discussed with a statistician prior to ethics lodgement.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2022
Actual
Date of last participant enrolment
Anticipated
30/06/2023
Actual
Date of last data collection
Anticipated
31/07/2024
Actual
Sample size
Target
54
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 19783 0
Liverpool Hospital - Liverpool
Recruitment postcode(s) [1] 34428 0
2170 - Liverpool

Funding & Sponsors
Funding source category [1] 308924 0
Commercial sector/Industry
Name [1] 308924 0
Merit Medical
Country [1] 308924 0
Australia
Funding source category [2] 312108 0
Commercial sector/Industry
Name [2] 312108 0
Terumo Medical Corporation
Country [2] 312108 0
Australia
Primary sponsor type
Hospital
Name
South Western Sydney Local health District
Address
South Western Sydney Local Health District Executive Office
Liverpool Hospital Eastern Campus
Scrivener Street
LIVERPOOL NSW 2170
Country
Australia
Secondary sponsor category [1] 309905 0
None
Name [1] 309905 0
Address [1] 309905 0
Country [1] 309905 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308814 0
South Western Sydney Local Health District
Ethics committee address [1] 308814 0
South Western Sydney Local Health District Executive Office
Liverpool Hospital Eastern Campus
Scrivener Street
LIVERPOOL NSW 2170
Ethics committee country [1] 308814 0
Australia
Date submitted for ethics approval [1] 308814 0
17/05/2022
Approval date [1] 308814 0
27/05/2022
Ethics approval number [1] 308814 0

Summary
Brief summary
Osteoarthritis (OA) is a chronic and progressive condition affecting 1 in 8 Australians. Recent advancement suggests that there is a vascular (formation of new vessels) and inflammatory component associated with OA.

Osteoarthritis of the knee is the most common form of OA. The risk of functional limitations from knee osteoarthritis is greater than that from any other medical condition for those aged 65 and above.

Blockage (embolisation) of these newly developed blood vessels in knee OA represents a method to reduce a patient's symptoms but also delay the progression of their condition. Across Japan, USA and UK, many researchers have looked at the safety and efficacy in carrying out embolisation of geniculate arteries. These studies have shown a reduction in patient’s pain and nil adverse outcomes associated with the procedure itself. This procedure represents a potential intermediate management tool with reduction in the costs associated with total knee replacements as well as increasing economic productivity for patients and the community.

This study hypothesises that patients who undergo blockage of the newly developed vessels will result in a reduction in analgesic consumption and an increase in quality of life for patients in comparison to the placebo.

This study aims to compare geniculate artery embolisation with non-procedural intervention to ascertain further data and aid the growing literature in the global community for the use of this procedure as a method to manage patients with osteoarthritis.

Participants will be assessed prior with a thorough clinical/medication history, physical examination and a questionnaire (visual analogue scale and Knee injury and osteoarthritis severity score) related to the patient’s experience with regards to their knee issues.

Once the participant has consented and enrolled in the study. The study will randomise participants into an intervention group (those that receive the blockage of vessels) and those that do not. Both participants will be followed up post procedure at the 1 day, 1 week, 1 month, 3-month, 6 month and 12-month mark for functional and subjective assessment of the knee.
Trial website
Trial related presentations / publications
Public notes


Okuno Y, Korchi AM, Shinjo T, et al. Transcatheter Arterial Embolization as a Treatment for Medial Knee Pain in Patients with Mild to Moderate Osteoarthritis. Cardiovasc Intervent Radiol 2015;38:336–43. doi:10.1007/s00270-014-0944-8

Okuno Y, Korchi AM, Shinjo T, et al. Midterm Clinical Outcomes and MR Imaging Changes after Transcatheter Arterial Embolization as a Treatment for Mild to Moderate Radiographic Knee Osteoarthritis Resistant to Conservative Treatment. J Vasc Interv Radiol 2017;28:995–1002. doi:10.1016/j.jvir.2017.02.033

Landers S, Hely A, Harrison B, et al. Protocol for a single-centre, parallel-arm, randomised controlled superiority trial evaluating the effects of transcatheter arterial embolisation of abnormal knee neovasculature on pain, function and quality of life in people with knee osteoarthritisBMJ Open 2017;7:e014266. doi: 10.1136/bmjopen-2016-014266

Contacts
Principal investigator
Name 111986 0
Dr Yehia El Hgar
Address 111986 0
Liverpool Hospital, Corner of Elizabeth and Goulburn Street, Liverpool, NSW 2127
Country 111986 0
Australia
Phone 111986 0
+61428355658
Fax 111986 0
Email 111986 0
[email protected]
Contact person for public queries
Name 111987 0
Dr Jasjit Walia
Address 111987 0
Liverpool Hospital, Corner of Elizabeth and Goulburn Street, Liverpool, NSW, 2127
Country 111987 0
Australia
Phone 111987 0
+6187383462
Fax 111987 0
Email 111987 0
[email protected]
Contact person for scientific queries
Name 111988 0
Dr Jasjit Walia
Address 111988 0
Liverpool Hospital, Corner of Elizabeth and Goulburn Street, Liverpool, NSW, 2127
Country 111988 0
Australia
Phone 111988 0
+61287383462
Fax 111988 0
Email 111988 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Once summation of results and interpretation of results has occurred, then these results will be published. Only aggregate results will be shared. No individual data results will be released.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.