Knee OsteoArthritis (KOA) is a common disease associated with pain and impaired function. Many patients are not relieved of their symptoms with enough efficacy by conservative treatments. Genicular Arteries Embolization (GAE) is a new minimally invasive endovascular treatment allowing symptoms relief. The investigator previously demonstrated the safety of GAE using an ethiodized oil-based emulsion for the treatment of painful knee osteoarthritis in a first-in-man single-arm clinical trial called LipioJoint-1 (clinicaltrials.gov: NCT04733092; EUDRACT: 2020-002206-10). This phase 1 study also provided encouraging evidence of GAE efficacy on knee pain and function.

The purpose of LipioJoint-2 study is to assess GAE efficacy using an ethiodized oil-based emulsion for the treatment of painful knee osteoarthritis in a multicenter, prospective, randomized sham-controlled clinical trial.

Patients will be screened during current practice consultation in each recruiting center (Screening Visit). When a patient will meet the eligibility criteria, he will be informed about the protocol.

The Interventional Radiologist will further explain the protocol to the patient and check inclusion/non-inclusion criteria during baseline visit. The date of signature of the informed consent by the patient will be considered as the date of inclusion. GAE (embolization) will be scheduled within the next few days.

Randomization will occur during the embolization visit, before patient is taken to the operating room. Randomization in a 2:1 ratio of GAE using emulsion to the sham procedure will be performed with stratification on Kellgren and Lawrence score (2-3 versus 4). All target arteries will be injected with an ethiodized oil-based emulsion (GAE group). Patient will be kept blind to the actual treatment using headphones or virtual headset.

Follow-up visits will be scheduled 1, 3, 6 and 12 months after randomization. Patient will be informed about his randomisation group (GAE or sham) after the completion of questionnaires (VAS pain, WOMAC, EQ-5D, HAD) at the 3-month visit and will be allowed to choose further medical & clinical management of his target KOA.

Inclusion Criteria:

• Diagnosis of primary KOA according to the classification of the American College of Rheumatology (ACR) (5)
• Radiographic Kellgren and Lawrence score ≥ 2 (6)
• VAS pain score ≥ 40 mm (scale 0-100 mm)
• Previous intra-articular injection in the target knee
• Patient not eligible to knee surgery
• For woman of childbearing potential: negative bêta-HCG before randomization
• Social security affiliation
• Signed informed consent
• Good understanding of the French language

Exclusion Criteria:

• Intra-articular injection of any product in the target joint within 3 months before embolization
• Prior knee surgery other than ligament repair
• Any inflammatory joint disease other than osteoarthritis
• Any contra-indication to puncture of the ipsilateral femoral artery
• Current treatment with cyclosporine, tacrolimus, cisplatine, vancomycine, amphotericine B or any aminoside
• Ipsilateral symptomatic hip OA
• Treated hyperthyroidism
• Known severe allergy to Lipiodol® and/or iodine contrast medium
• Known moderate to severe kidney failure (creatinine clearance < 30 45 ml/min)
• Known right-to-left cardiac shunt or intra-tumoral vascular shunt
• Asthma attack in the 8 days before randomization
• Exploration or treatment with radioactive iodine scheduled within 1 month after randomization
• Symptomatic atheromatous lesion in the ipsilateral limb
• Patient unable or unwilling to comply with the follow-up schedule (at the investigator's discretion)
• Vulnerable populations (such as pregnant or breastfeeding women, patient under guardianship curatorship, deprived of liberty)
• Patient under exclusion period in another trial
• Patient on AME (state medical aid)

Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared.

Two years after the last publication

Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered.

Teams wishing obtain IPD must meet the sponsor and PI team to present scientifics (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractualization.

Processing of shared data must comply with European General Data Protection Regulation (GDPR).

Only the personal of the Interventional Radiology department of HEGP (only unblinded center) will have the knowledge of the trial arm.

Patient will be blinded from randomization arm using headphones and/or virtual headset.

The research personnel will be trained accordingly and will keep a separate file with patient's images to ensure that they are not transferred on the Pacs system (Carestream).

The research assistant will discard the products after completion of the procedure in specific containers, that will not be accessible to the patient or to nurses and technicians directly involved in the current patient's care.

Patient's blindness will be assessed using a blinding index after GAE and at the 3-month follow-up visit. The proposed blinding index is scaled to an interval of -1 to 1, 1 being complete lack of blinding, 0 being consistent with perfect blinding and -1 indicating opposite guessing which may be related to unblinding.