Knee Osteoarthritis
Conditions
Keywords
Embolization, Pain, Randomized sham-controlled trial
Brief summary
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.
Detailed description
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.
Interventions
DRUGEthiodized Oil-based emulsion
Embolization of genicular arteries
PROCEDURESham-operation
Mimicked catheterization and embolization of genicular arteries
Sponsors
Ministry of Health, France
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
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.
Intervention model description
Randomized, single-blind, multicenter trial comparing GAE using an ethiodized oil-based emulsion with a sham procedure in patients with symptomatic knee osteoarthritis. Randomization in a 2:1 ratio of GAE using an ethiodized oil-based emulsion to the sham procedure will be performed with stratification on Kellgren and Lawrence score (2-3 versus 4).
Eligibility
Sex/Gender
ALL
Age
40 Years to 90 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of pain assessed by a Visual Analogue Scale (VAS) at 3 months compared to randomization. | 3 months | VAS pain is a validated, self-reported instrument assessing average pain over the past 48 hour period. Score ranges from 0 (no pain) to 100 (worst possible pain). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of pain assessed by a Visual Analogue Scale (VAS) at 6 months compared to randomization. | 6 months | VAS pain is a validated, self-reported instrument assessing average pain over the past 48 hour period. Score ranges from 0 (no pain) to 100 (worst possible pain). |
| Change of pain assessed by a Visual Analogue Scale (VAS) at 12 months compared to randomization. | 12 months | VAS pain is a validated, self-reported instrument assessing average pain over the past 48 hour period. Score ranges from 0 (no pain) to 100 (worst possible pain). |
| Description of target knee events in both groups at 6 and 12 months. | Up to 12 months | Events of interest includes intra-articular injections, embolization, surgery. |
| Incremental efficiency of genicular arteries embolization compared to sham treatment (medico-economic analysis). | 6 months | Medico-economic study: incremental cost utility ratio |
| Change of the patient's global assessment of her/his health measured by the Visual Analogue Scale of EQ-5D questionnaire (EQ VAS) at 1, 3, 6, 12 months compared to randomization. | Up to 12 months | EQ-5D questionnaire is a validated, self-reported instrument assessing today health-related quality of life. EQ VAS is the second part of EQ-5D, consisting in a Visual Analogue Scale of health. Score ranges from 0 (worst health) to 100 (best health). |
| Change of the Western Ontario and McMaster Universities Arthritis (WOMAC) total and sub-scores (pain, function,stiffness) at 1, 3, 6, 12 months compared to randomization. | Up to 12 months | WOMAC questionnaire is a validated, self-reported instrument assessing the daily condition of patients with osteoarthritis of the lower limb. It has a multidimensional scale comprising 24 items grouped into three dimensions: pain (5 items), stiffness (2 items), and physical functioning (17 items). Likert scale will be normalized to 100. Scores ranges from 0 (no impairment) to 100 (severe impairment). |
| Change of the Knee injury and Osteoarthritis Outcome Score (KOOS) total and sub-scores at 3 months compared to randomization. | 3 months | KOOS questionnaire is a validated, self-reported instrument assessing the daily condition of patients with osteoarthritis of the lower limb. It has a multidimensional scale comprising 42 items grouped into five dimensions: pain (9 items), symptoms (7 items), activities of daily living function (17 items), sport and recreation function (5 items), quality of life (4 items). A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as common in orthopedic assessment scales and generic measures. |
| Change of pain assessed by a Visual Analogue Scale (VAS) at 1 month compared to randomization. | 1 month | VAS pain is a validated, self-reported instrument assessing average pain over the past 48 hour period. Score ranges from 0 (no pain) to 100 (worst possible pain). |
| Change of semi-quantitative MRI scoring at 6 months compared to randomization. | 6 months | Semi-quantitative MRI scoring may include Whole-Organ Magnetic Resonance Imaging Score (WORMS), Knee Osteoarthritis Scoring System (KOSS), Boston-Leeds Osteoarthritis Knee Scoring (BLOKS), MRI Osteoarthritis Knee Score (MOAKS). |
| Description of pain medication at Month 1, 3, 6, 12. | Up to 12 months | Pain medication will be described using analgesic level. |
| Description of non-pharmacological treatments for target knee in both groups at 1, 3, 6, and 12 months. | Up to 12 months | Non-pharmacological interventions may include, but are not limited to, physiotherapy, osteopathy, acupuncture, massage, electroanalgesia, laser therapy, low-level light therapy, meditation. |
| Number of responder patients under OMERACT-OARSI definition in both groups at 3, 6 and 12 months. | Up to 12 months | A patient is defined as responder under OMERACT-OARSI criteria if one of the following conditions is satisfied: * Improvement in pain (0-100 mm VAS) or in WOMAC function score ≥50% and absolute change ≥20 is observed or * Improvement in at least 2 of the 3 following conditions: * Pain (0-100 mm VAS) ≥20% and absolute change ≥10 * WOMAC function score ≥20% and absolute change ≥10 * Patient's global assessment of her/his health (0-100 mm EQ-5D VAS) ≥20% and absolute change ≥10 |
| Number of patients reaching an acceptable symptom state (PASS) in both groups at 3, 6, and 12 months. | Up to 12 months | PASS is defined for each patient reported outcome as: * Pain (0-100 mm VAS) ≤32.3, * Patients global assessment of her/his health (0-100 mm EQ-5D VAS) ≤32, * WOMAC function score (0-100) ≤31. |
| Number and description of adverse events and serious adverse events at 1, 3, 6 and 12 months. | Up to 12 months | Adverse events are defined according to Article 2 of the Regulation (EU) No 536/2014. Intensity of adverse events will be graded using Clavien-Dindo classification and CTCAE v 5.0. |
| Change of the Hospital Anxiety and Depression (HAD) score and sub-scores at 3 months compared to randomization. | 3 months | HAD questionnaire is a validated, self-reported instrument assessing the levels of anxiety and depression. It has a multidimensional scale comprising 14 items grouped into two dimensions: anxiety (7 items), and depression (7 items). Scoring for each item ranges from zero to three, with three denoting highest anxiety or depression level. Total score ranges from 0 (no impairment) to 42 (severe impairement). A total sub-scale score of \>8 points out of a possible 21 denotes considerable symptoms of anxiety or depression. |
Countries
France
Contacts
Primary ContactTouria EL AAMRI
Backup ContactCléo BOURGEOIS
Outcome results
None listed