Genicular Artery Embolisation for Knee Osteoarthritis II

Official title

Genicular artEry embolisatioN in patiEnts With oSteoarthrItiS of the Knee II

Overview

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.

Interventions

• Procedure Genicular Artery Embolisation
  Transarterial catheter directed embolisation of hypervascularity in patients with mild to moderate knee osteoarthritis
• Procedure Genicular Artery Injection
  Transarterial catheter directed injection of normal (0.9%) saline in patients with mild to moderate knee osteoarthritis

Primary outcome measures

• Determine if embolisation of abnormal neovasculature arising from branches of the genicular arteries reduces pain in patients with knee OA compared to Sham treatment [Time frame: 6 months]

Secondary outcome measures (3)

• Determine clinical success [Time frame: 6 months]
• Assessment of pain relief [Time frame: 6 months]
• Determine if embolisation improves pain, function, and quality of life in patients with knee OA compared to Sham treatment [Time frame: 6 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Treatment

Study locations

United Kingdom · 1 center

• Royal Berkshire NHS Foundation Trust — Reading

Publications

• Little MW, Harrison R, MacGill S, Speirs A, Briggs JH, Tayton E, Davies NLC, Hausen HS, McCann C, Levine LL, Sharma RA, Gibson M. Genicular Artery Embolisation in Patients with Osteoarthritis of the Knee (GENESIS 2): Protocol for a Double-Blind Randomised Sham-Controlled Trial. Cardiovasc Intervent Radiol. 2023 Sep;46(9):1276-1282. doi: 10.1007/s00270-023-03477-z. Epub 2023 Jun 19. PMID 37337060

Identifiers

NCT: NCT05423587 · VAR-2021-11 · 286849

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗