Clinical trial NCT05423587: Genicular Artery Embolisation for Knee Osteoarthritis II
Official title: Genicular artEry embolisatioN in patiEnts With oSteoarthrItiS of the Knee II
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Knee Osteoarthritis
Keywords: Microspheres
Embozene
Artery Embolization
Joint diseases
Osteoarthritis, Knee
Lead sponsor: Varian, a Siemens Healthineers Company
Sponsor class: INDUSTRY
First posted: 2022-06-21
Enrollment: 110
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Single Site, Double Blind Sham Randomized Controlled Trial with Sham subject optional crossover to the treatment arm (GAE) at 6 months post randomization to determine if embolization of abnormal blood vessels arising from branches of the genicular arteries reduces pain in patients with knee osteoarthritis.
Primary purpose: TREATMENT

Brief summary: This clinical study is designed as a double-blind sham controlled randomised trial with the option of sham group crossover to receive the GAE treatment at 6 months after unblinding. This study will determine if embolisation of abnormal neovasculature arising from branches of the genicular arteries reduces pain in patients with knee osteoarthritis. The study patient population will consist of up to 110 subjects with knee pain for at least 3 months that is resistant to conservative treatment measures. Subjects will be treated with knee embolisation or 2 mL of saline in the sham arm. At 6 months, all subjects in the sham arm will be allowed to cross-over and receive the embolisation procedure with a follow-up duration of 18 months. The total planned study duration is 3.5 years.

Detailed description: This is a single-center, randomised trial to compare patients who receive genicular artery embolisation of the knee with patients who receive a sham procedure with saline injection.

The study population will consist of up to 110 subjects with knee pain that is resistant to conservative treatment measures for at least 3 months. Subjects will be followed for 24 months. At 6 months patients will be unblinded and offered an optional crossover to receive the GAE procedure with 18 months follow-up.

Alongside a sham surgery placebo arm, a high-quality systematic review of surgical RCTs was used as a suitable benchmark to inform the sample size and power calculation.

With a 0-100 scale for the primary endpoint of KOOS4, assuming a 1:1 randomization, a mean difference of 6.4 (i.e., effect size) between GAE and Sham treatments, a common standard deviation of 10 (i.e., a Cohen's D of 0.64), an alpha error of 2-sided 0.05 and a power of 0.85, the 2-arm total sample size the requirement is 88 subjects (44 each arm) by Normal approximation. Allowing for a participant dropout rate of 20%, the enrolment goal is 110 participants, approximately 55 in each study arm.

All study subjects will undergo a physical exam and history, a contrast-enhanced knee MRI, blood serum and neuropschological assessment with a functional head MRI to identify potential predictors of treatment success.

In the GAE treatment arm subject will undergo a genicular artery embolization with Embozene microspheres (100 micron) (Varian Medical Systems) and the Sham group will receive saline through the transarterial catheter through groin access.

Participants will be randomly assigned to have particulate embolisation with 100-micron Embozene particles, or to injection with 2 ml heparinized normal saline (sham arm) At 6 months participants will be unblinded and there will be an open extension period for 6 months, in which participants in the sham arm will be offered GAE.

Follow-up visits will be at 1 month, 3 months, 6 months, 12 months and 24 months post randomisation. At these visits subjects will complete the KOOS score, the visual analog scale (VAS) pain score, an analgesia diary, and at specific time points the EQ-5D-3L, and report any new adverse events (AEs).All subjects will undergo a contrast-enhanced knee MRI at baseline and at 6 and 12 months.

At 6 months after unblinding the sham group subjects have the option to cross over and receive the GAE treatment with follow-up at 1 month, 3 months, 6 months, 12 months and 18 months.

Eligibility criteria: Inclusion Criteria:

ALL inclusion criteria below need to be fulfilled for the patient to participate in the study.

* Participant is willing and able to give informed consent for participation in the study.
* Participants aged 45 years or above.
* Grade 1-3 knee OA on X-ray as per Kellgren-Lawrence Grading Scale
* Knee pain for at least 3 months resistant to conservative non-surgical treatment (e.g., physiotherapy, steroid injections, weight loss programs, PRP (platelet-rich plasma) injections)
* Be able to lie flat for at least 6 hours-this will be assessed by asking how participants sleep (bed, chair recumbent, semi-recumbent) and assessing what prevents them from lying flat overnight (breathlessness, back pain, etc)
* Minimum score of 50 on baseline 0 - 100 VAS

Exclusion Criteria:

The patient may not enter the study if ANY of the following apply:

* Rheumatoid arthritis or infectious arthritis
* Severe knee OA (grade 4 on x-ray as per Kellgren-Lawrence Grade)
* Renal impairment: eGFR \<45. Assessed from medical records or a blood test if required as is part of standard clinical practice when considering a patient for a therapeutic intervention.
* Patients with a bleeding diathesis, or other bleeding risk such as patients on warfarin which cannot be stopped easily (e.g., patients with metallic heart valves) assessed by asking the patient and from medical records. Uncorrectable bleeding diathesis: INR\>1.6, Platelets \<50,000
* Requires oxygen on ambulation. Assessed by asking the patient and from medical records.
* Low life expectancy (\<1 year)
* Communication difficulty due to language barriers
* Contraindication to MRI
* Known allergies to barium sulfate, 3-aminopropyltrialkoxysilane, polyphosphazene or IV radiopaque contrast agent
* History of Peripheral Arterial Disease (PAD) with intermittent claudication and/or rest pain
* Pregnancy or positive pregnancy test (the participant will be exposed to ionising radiation during the fluoroscopy procedure)
* Any other significant disease or disorder which, in the opinion of the recruiting physician, may put the participants at risk because of participation in the study, or may influence the result of the study or the participant's ability to participate

Primary outcomes:
measure: Determine if embolisation of abnormal neovasculature arising from branches of the genicular arteries reduces pain in patients with knee OA compared to Sham treatment
timeFrame: 6 months
Secondary outcomes:
measure: Determine clinical success
timeFrame: 6 months
measure: Assessment of pain relief
timeFrame: 6 months
measure: Determine if embolisation improves pain, function, and quality of life in patients with knee OA compared to Sham treatment
timeFrame: 6 months
Other outcomes:
measure: Determine safety and toxicity
timeFrame: 6 months follow-up
measure: Determine if improvement of knee osteoarthritis can be described by imaging analysis following GAE vs Sham
timeFrame: 6 months
measure: Quantification of a personalised psychometric pain profile to determine whether treatment response can be predicted using behavioural indicators of predisposition to central facilitation of pain
timeFrame: 6 months
measure: Determine quality of life changes
timeFrame: 6 months
measure: Assess patient reported acceptability of study treatment
timeFrame: 1 week after treatment
measure: Determine if patient's need for analgesia will be reduced
timeFrame: 6 months
measure: Assess durability of GAE
timeFrame: 24 months
measure: Perform a health economic cost effectiveness analysis of GAE versus other treatment modalities in the moderate knee OA space
timeFrame: 6 months
measure: Determine if embolisation improves pain, function, and quality of life in patients with knee OA in the treatment group
timeFrame: 24 months follow-up
measure: Determine quality of life changes in the GAE group at 12 and 24 months
timeFrame: 24 months follow-up
measure: Describe imaging outcomes of knee at 12 months in GAE
timeFrame: 12 months
measure: Determine if patient's need for analgesia will be reduced in the GAE group
timeFrame: 24 months
measure: Assessment of pain relief in the GAE group
timeFrame: 24 months
measure: Determine if embolisation improves pain, function, and quality of life in patients with knee OA in the treatment group and compare with the Sham group in subjects who do not cross over at 12 and 24 months
timeFrame: 24 Months
measure: Determine quality of life changes in the GAE and sham group
timeFrame: 24 months
measure: Determine if patient's need for analgesia will be reduced
timeFrame: 24 months
measure: Assessment of pain relief
timeFrame: 24 months
measure: Determine if embolisation improves pain, function, and quality of life in patients with knee OA in the Sham crossover group at 1, 3, 6, 12 and 18 months
timeFrame: 18 months
measure: Assessment of pain relief in the Sham crossover group
timeFrame: 18 months
measure: Determine if patient's need for analgesia will be reduced in the Sham crossover group
timeFrame: 18 months
measure: Determine quality of life changes in the Sham crossover group
timeFrame: 18 months
measure: Determine if improvement of knee osteoarthritis can be described by imaging analysis in the Sham crossover group following GAE
timeFrame: 12 months
measure: Quantification of mindfulness as part of a personalised psychometric pain profile to determine whether treatment response can be predicted using behavioural indicators of predisposition to central facilitation of pain
timeFrame: 6 months
measure: Assessment of depressive symptoms as part of a personalised psychometric profile
timeFrame: 6 months
measure: Assessment of patient's psychological flexibility as part of personalised psychometric profile
timeFrame: 6 months
measure: Assessment of a patient's anxiety as part of a personalised psychometric profile
timeFrame: 6 months
measure: Quantification of patient's psychological flexibility as part of a personalised psychometric profile
timeFrame: 6 months
measure: Quantification of a patient's intolerance of uncertainty
timeFrame: 6 months
measure: Quantification of a patient's sleep quality as part of personalised psychometric profile
timeFrame: 6 months
measure: Assessment of psychological inflexibility in pain as part of a personalised psychometric pain profile to determine whether treatment response can be predicted using behavioural indicators of predisposition to central facilitation of pain
timeFrame: 6 months
measure: Quantification of the perspective of a participant's viewpoint on pain as part of a personalised psychometric pain profile
timeFrame: 6 months
measure: Behavioural quantification of psychological flexibility to stratify patients who achieve optimal clinical outcomes from the treatment procedure.
timeFrame: 6 months
measure: Assess functional connectivity between brain regions and investigate the influence of metabolite levels within pain modulatory regions as a neurochemical marker for vulnerability to further chronic pain states.
timeFrame: 6 months
measure: Assess patient's capacity of central pain modulation
timeFrame: 6 months
measure: Assess patient's intrinsic attention to pain
timeFrame: 6 months
measure: Assess patient's capacity of central facilitation of pain
timeFrame: 6 months
measure: Perception of health by patient in the GAE and sham group
timeFrame: 6 months
measure: Perception of health by patient in the GAE group
timeFrame: 24 months follow-up
measure: Perception of health by patient in GAE and sham group at 12 and 24 months
timeFrame: 24 months
measure: Perception of health by patient in sham crossover group at 6, 12 and 18 months
timeFrame: 18 months
Locations:
city: Reading
country: United Kingdom
facility: Royal Berkshire NHS Foundation Trust
Study officials:
affiliation: Royal Berkshire NHS Foundation Trust, Reading, UK
name: Mark W Little, MD
role: PRINCIPAL_INVESTIGATOR
References: