Patient case (clinical description): A 47-year-old woman comes to the office complaining of pain in the calf and knee when she bends down. The pain limits her activity. Her medical history is significant for osteoarthritis, for which she uses nonsteroidal anti-inflammatory drugs (NSAIDs) for the past two years. She is living with her husband and has 3 children. She doesn't smoke but drinks alcohol occasionally. Her vital signs are normal. On physical examination, there is a small effusion in the right knee. The effusion grew a little larger and she developed a tender swelling in the popliteal fossa and calf. Both the pain and swelling worsened as she bent and straightened her knee.

Patient's own account: I'm a 47-year-old woman, married with 3 kids. I don't smoke and I drink occasionally. I went to the doctor because of pain in my calf and knee when I was bending down. This has been limiting my daily activities. I have been diagnosed with osteoarthritis for which I have taken anti-inflammatory drugs for the past 2 years. The doctor saw a small fluid buildup in my right knee. This buildup became a bit bigger and I have a swollen calf. The pain is worse when I bend and straighten my knee.

Clinical trial: Pilot, Prospective, Comparative Multicentric Study Evaluating the Effects on the Arthrosis Biomarkers, the Clinical Effectiveness, the Tolerance of an Intra-articular Injection of Hyaluronic Acid KARTILAGE CROSS Versus Placebo in Patients Suffering From Knee Osteoarthritis

Eligibility criteria:
Inclusion Criteria:

          -  Man or Women, aged from 45 to 80

          -  Presenting a symptomatic femoro-tibial knee osteoarthritis responding to clinical and
             radiologic ACR (American College of Rheumatology) criteria,

          -  Symptomatic since at least 6 months

          -  Mean global knee pain determined on Visual Analog Scale for the last 24 hours over 40
             mm (without any NSAIDs or analgesics for more than 48 hours).

          -  Kellgren and Lawrence (K&L) radiological stage must have been II or III on pictures
             lasted less than 12 months

          -  Requiring a treatment with hyaluronic acid after failure or intolerance to first line
             analgesics or NSAIDs

          -  Having signed an informed consent after receiving comprehensive information

          -  Capable to follow the study instructions

          -  Benefiting from health insurance.

        Exclusion Criteria:

        Related to the osteoarthritis pathology:

          -  Significant clinical knee effusion

          -  Radiographical Kellgren and Lawrence grade I or IV

          -  Osteoarthritis secondary to a microcrystalline arthropathy: chondrocalcinosis
             previously known or defined by a calcium border on at least one tibiofemoral spacing,
             gout ...

          -  Isolated femoropatellar osteoarthritis

          -  Presence of another joint (other than the evaluated knee) affected by osteoarthritis
             (known and symptomatic): collateral knee, hip, hand, shoulder, ankle or foot

          -  Chondromatosis or villonodular synovitis of the knee

          -  Paget disease

          -  Recent trauma (< 1 month) of the evaluated knee

          -  Pathologies interfering with the evaluation of osteoarthritis (microcrystalline
             inflammatory arthropathy, rheumatoid arthritis, radiculalgia in the lower limbs,
             arteritis. etc)

          -  Acute inflammatory osteoarthritis (Kofus ≥ 7)

        Related to previous and concomitant treatments

          -  Corticosteroids injection in the last month before injection regardless the concerned
             joint

          -  Hyaluronan injection in the last 6 months before injection regardless the concerned
             joint

          -  Analgesics and NSAIDs intake during the last 48 hours before inclusion visit

          -  Change in the dosage of slow-acting drugs against arthrosis i.e. chondroitin,
             glucosamine, diacerein or avocado-soybean unsaponifiables in the last 3 months before
             inclusion or planned during study

          -  Arthroscopy or surgery in the target knee in the last 3 months before inclusion

          -  Oral corticotherapy

        Related to associated pathologies

          -  Severe diseases (severe hepatic failure, renal failure, uncontrolled cardiovascular
             diseases….)

          -  Dermatological infection at the site of injection

          -  Anticoagulant treatment

          -  Risk of hemorrhage according to the evaluator or injector assessment

        Related to the patients

          -  Known allergy to hyaluronan

          -  Known allergy to acetaminophen

          -  Known allergy to mannitol

          -  Pregnant or breastfeeding women

          -  Premenopausal women without contraception

          -  Patient unable to read, and to write

          -  Patient having participated in a clinical research investigation in the last 3 months

          -  Patient under guardianship or judicial protection
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 45 Years old.
Subject must be at most 80 Years

Eligibility (NLI label): Entailment