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Trial registered on ANZCTR


Registration number
ACTRN12616001184460
Ethics application status
Approved
Date submitted
7/06/2016
Date registered
29/08/2016
Date last updated
26/08/2019
Date data sharing statement initially provided
26/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluating transcatheter arterial embolisation for improvement of pain in osteoarthritis (OA) of the knee
Scientific title
Evaluating transcatheter arterial embolisation for improvement of pain in OA of the knee – a randomised controlled trial
Secondary ID [1] 289359 0
Nil known
Universal Trial Number (UTN)
U1111-1183-8503
Trial acronym
EIEIO
Linked study record
ACTRN12616000770460

Health condition
Health condition(s) or problem(s) studied:
Knee osteoarthritis 298992 0
Condition category
Condition code
Musculoskeletal 299056 299056 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants in the treatment group will have abnormal blood vessels about the study knee embolised. Participants will receive a local anaesthetic injected (1% lignocaine) into their groin. Femoral artery access will be obtained with a 3French sheath and a micro-catheter introduced. Digital subtraction angiography using contrast (iodine-containing contrast medium) will be obtained of the knee identifying abnormal neovasculature arising from the genicular arterial branches. The abnormal vessels will be embolised with a suspension of 0.5 g of Imipenem and cilastatin sodium (IPM-CS)(Primaxin; Merck & Co. Inc., Whitehouse Station, NJ, USA) in 5mL of iodinated contrast agent (prepared by pumping syringes for 10 seconds) will be injected in 0.2mL increments until blood flow stagnates.

The guide wire will be removed. A dressing will be applied to the puncture site.

All procedures will be conducted by a fully qualified interventional radiologist who is trained to perform vascular embolisation.

The procedure is expected to take 30-60minutes depending on the number of vessels embolised.
Intervention code [1] 294944 0
Treatment: Surgery
Intervention code [2] 294999 0
Treatment: Devices
Comparator / control treatment
Participants in the control group will receive a placebo intervention. Participants will receive a local anaesthetic injection (1% lignocaine) and an incision into their groin. The radiologist will then pretend to insert a guide wire and catheter into the blood vessel and complete the embolisation procedure. Pre-recorded video images will be displayed on the monitor that the patient can see showing an embolization procedure being completed. No wire or catheter will be introduced. No contrast will be administered. No radiation will be utilised. The duration of the placebo procedure will match that of the treatment arm. A dressing will be applied to the incision site.

All procedure will be conducted by a fully qualified interventional radiologist who is trained to perform vascular embolisation.
Control group
Placebo

Outcomes
Primary outcome [1] 298529 0
Change in knee pain as assessed by the Knee injury and Osteoarthritis Outcome Score (KOOS),
Timepoint [1] 298529 0
1 year post intervention
Secondary outcome [1] 324471 0
Change in knee pain as assessed by the Knee injury and Osteoarthritis Outcome Score (KOOS),
Timepoint [1] 324471 0
1 and 6 months post intervention for the placebo group.
1, 6 and 24 months post intervention for the intervention group.
Secondary outcome [2] 324472 0
Change in self-reported physical function as measured by the KOOS Function Daily Living scale and KOOS Function, Sports and Recreational Activities scale
Timepoint [2] 324472 0
1, 6 and 12 months post intervention for the placebo group.
1, 6, 12 and 24 months post intervention for the intervention group.
Secondary outcome [3] 324473 0
Change in self-reported joint stiffness as measured by the KOOS Stiffness scale
Timepoint [3] 324473 0
1, 6 and 12 months post intervention for the placebo group.
1, 6, 12 and 24 months post intervention for the intervention group.
Secondary outcome [4] 324476 0
Change in self-reported quality of life as measured by the EuroQol EQ-5D-5L and KOOS Quality of life scale
Timepoint [4] 324476 0
1, 6 and 12 months post intervention for the placebo group.
1, 6, 12 and 24 months post intervention for the intervention group.
Secondary outcome [5] 324477 0
Self-reported global overall change (7 point ordinal scale)
Timepoint [5] 324477 0
1, 6 and 12 months post intervention for the placebo group.
1, 6, 12 and 24 months post intervention for the intervention group.
Secondary outcome [6] 324478 0
Change in six minute walk test performance
Timepoint [6] 324478 0
1, 6 and 12 months post intervention for the placebo group.
1, 6, 12 and 24 months post intervention for the intervention group.
Secondary outcome [7] 324479 0
Change in pharmacotherapy usage (patient report of the frequency and dosage of medication) for knee pain secondary to OA
Timepoint [7] 324479 0
1, 6 and 12 months post intervention for the placebo group.
1, 6, 12 and 24 months post intervention for the intervention group.
Secondary outcome [8] 324651 0
Self-reported global overall change in knee pain (7 point ordinal scale)
Timepoint [8] 324651 0
1, 6 and 12 months post intervention for the placebo group.
1, 6, 12 and 24 months post intervention for the intervention group.
Secondary outcome [9] 324652 0
Self-reported global overall change in physical function (7 point ordinal scale)
Timepoint [9] 324652 0
1, 6 and 12 months post intervention for the placebo group.
1, 6, 12 and 24 months post intervention for the intervention group.
Secondary outcome [10] 324653 0
Change in 30 second chair stand test performance
Timepoint [10] 324653 0
1, 6 and 12 months post intervention for the placebo group.
1, 6, 12 and 24 months post intervention for the intervention group.

Eligibility
Key inclusion criteria
1. People aged 18 to 75 years
2. Grade 2 knee OA (obtained via baseline imaging (X-Ray) as per Kellgren-Lawrence Grading Scale)
3. Moderate to severe knee pain
4. Knee pain for at least six months
5. Pain resistant to conservative treatment
a. Conservative treatment includes medication (e.g. paracetamol, anti-inflammatories), or intra-articular injections, or physiotherapy or exercise, or weight loss.
6. Participants must be willing, able and mentally competent to provide informed consent (able to read and understand the Patient Information and Consent Form)
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Local infection
2. Active malignancy
3. Rheumatoid Arthritis or Seronegative Arthropathies
4. Prior Ipsilateral Knee Surgery
5. Kellgren-Lawrence Grade 3 and above
6. Current pregnancy
a. If participant is unsure of their current pregnancy status clarification from their GP including arranging a pregnancy test and following up the result can be obtained
7. Known history of allergy to contrast media
8. Weight greater than 200kg
9. Barwon Medical Imaging Protocols:
a.Platelets < 100 x 109/L
b. INR > 1.5
c. Estimated GFR < 30ml/min.1.73m2
10. Approved for knee joint replacement surgery
11. Moderate to severe pain in other lower limb joints
12. History of allergy to carbapenem (e.g. imipenem, ertapenem or meropenem), or having an immediate or severe hypersensitivity reaction to a penicillin or cephalosporin antibiotic
13. History of seizures or using valproate

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)
Group assignment will be computer generated and informed using REDCap (Research Electronic Data Capture) online software. The interventionalist will access each participant's group allocation immediately prior to each intervention by logging into REDCap and running the allocation process.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The allocation schedule will be generated by the trial statistician prior to trial commencement via random block allocation. The allocation schedule will be developed and disseminated via REDCap (Research Electronic Data Capture) online software. The allocation schedule will be unknown to the members of the research team with the exception of the interventionalist who will access each individual's allocation immediately prior to the intervention.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Analysis will be performed on an intention-to-treat basis including all randomised participants.

The primary analysis will be performed on the transformed KOOS pain scale, using percentage reduction from baseline and a two-sample t-test if no dropout occurs and all 12 month data is available on each participant. Normality of the outcomes will be assessed, and if the assumptions are not met, the primary analysis will be conducted using the Wilcoxon rank sum test.

In the case of dropouts or missing data at 12 months, the primary analysis will be conducted under a linear regression model, with random effects accounting for intra-individual correlations.

Secondary outcomes:
Outcome data that is available at multiple time points will also be analysed using linear regression model, with random effects accounting for intra-individual correlations. Differences between intervention and placebo arms will be analysed and presented for each timepoint using a time-by-intervention product term.

Sample size calculations
The sample size was calculated on the basis of the primary hypothesis. Using data provided by Okuno et al (Okuno et al, 2015), we estimate that the standard deviation of change in pain is 19.9%. Given the small sample size, and the observational nature of Okuno et al (Okuno et al, 2015) we have chosen to take a more conservative approach and use the upper limit of the 80% confidence interval for the standard deviation. This standard deviation was calculated via bootstrapping and was equal to 23.9%.

For the mean difference in change in pain we use a minimal clinically significant difference (MCSD) of 20%.

To detect a mean difference in change in pain of 20% (s.d. = 23.9%) with a two-sided significance level of a=5% and power of 80% using a two-sample t-test, we require 24 participants per arm. Allowing for 20% drop out, 29 participants per arm will be recruited, i.e. 58 participants in total.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 5913 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment postcode(s) [1] 13360 0
3220 - Geelong

Funding & Sponsors
Funding source category [1] 293752 0
Other
Name [1] 293752 0
Barwon Medical Imaging
Address [1] 293752 0
c/o University Hospital Geelong,
PO Box 281
Geelong, Victoria, Australia, 3220
Country [1] 293752 0
Australia
Primary sponsor type
Other
Name
Barwon Medical Imaging
Address
c/o University Hospital Geelong,
PO Box 281
Geelong, Victoria, Australia, 3220
Country
Australia
Secondary sponsor category [1] 292581 0
None
Name [1] 292581 0
Address [1] 292581 0
Country [1] 292581 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295189 0
Barwon Health Human Research Ethics Committee
Ethics committee address [1] 295189 0
Research Ethics Governance and Integrity Unit
Barwon Health
PO Box 281
Geelong, Victoria, Australia, 3220
Ethics committee country [1] 295189 0
Australia
Date submitted for ethics approval [1] 295189 0
25/08/2015
Approval date [1] 295189 0
30/05/2016
Ethics approval number [1] 295189 0

Summary
Brief summary
Knee osteoarthritis (OA) is a leading cause of pain and disability around the world. OA involves the breakdown of joint cartilage, but it also appears to include the proliferation of blood vessels and nerves about the joint. It is suggested that these blood vessels and nerves contribute to the experience of pain. One pilot study found that embolising abnormal vessels about the knee substantially improved individual's pain.

The primary aim of the current study is to determine whether transcatheter arterial embolisation of abnormal neovasculature about the knee improves pain. Secondary aims include whether embolisation improves physical function, quality of life, joint stiffness, and medication usage.

The study is a randomised controlled trial. People are eligible if they have knee OA that is not yet ready for knee replacement surgery and have tried other forms of traditional management such as medications and physiotherapy.

Participants will be randomly allocated to one of two groups: intervention or placebo. Participants in the intervention group will receive embolisation of abnormal vessels about the knee. Participants in the control group will receive a placebo intervention that looks and feels like the real intervention but does not include embolisation of abnormal blood vessels.

All participants will be assessed shortly before the intervention (real or placebo) and then 1, 6 and 12 months after the intervention. Participants in the intervention group will also be assessed 24 months following the intervention. Assessment includes a variety of questionnaires and physical tests.
Trial website
None
Trial related presentations / publications
None
Public notes

Contacts
Principal investigator
Name 66394 0
Dr Steve Landers
Address 66394 0
c/o Barwon Medical Imaging
Barwon Health
PO Box 281
Geelong, Victoria, Australia,
3220
Country 66394 0
Australia
Phone 66394 0
+61 3 42150000
Fax 66394 0
Email 66394 0
stevel@barwonhealth.org.au
Contact person for public queries
Name 66395 0
Ms Rachael Hely
Address 66395 0
c/o Barwon Medical Imaging
Barwon Health
PO Box 281
Geelong, Victoria, Australia
3220
Country 66395 0
Australia
Phone 66395 0
+61 3 42150000
Fax 66395 0
Email 66395 0
Rachaehe@barwonhealth.org.au
Contact person for scientific queries
Name 66396 0
Dr Stephen Gill
Address 66396 0
c/o Barwon Medical Imaging
Barwon Health
PO Box 281
Geelong, Victoria, Australia
3220
Country 66396 0
Australia
Phone 66396 0
+61 3 42150000
Fax 66396 0
Email 66396 0
steveg@barwonhealth.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
We are yet to confirm our data sharing plans
What supporting documents are/will be available?
Study protocol
How or where can supporting documents be obtained?
Type [1] 4043 0
Study protocol
Citation [1] 4043 0
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 osteoarthritis BMJ Open 2017;7:e014266. doi: 10.1136/bmjopen-2016-014266
Email [1] 4043 0
Other [1] 4043 0
Attachment [1] 4043 0
Summary results
No Results