Table 1 Inclusion and exclusion criteria

Inclusion criteria

• Men or women, age 45–75;

• Medial femoro-tibial gonarthrosis (in case of bilateral OA, the most painful knee was evaluated);

• Responding to ACR criteria (clinical evaluation and radiological);

• Symptoms lasting for more than 6 months;

• Global knee pain evaluation over the last 24 hours > 40 mm (without NSAID or other analgesic for more than 48 hours);

• K&L II to III (Kellgren and Lawrence evaluated within the last 12 months);

• Agreed to banish NSAIDs and analgesics for the duration of the study;

• Signed informed consent;

• Capable of following the study guidelines;

• With health insurance.

Exclusion criteria

Patients with AT LEAST ONE of the following criteria were not enrolled in the study

• OA disease:

  o Secondary OA due to metabolic arthropathy: chondrocalcinosis previously

  o Known or defined by a calcium border on at least one tibiofemoral joint space, gout,…

  o Predominant symptomatic femoropatellar OA;

  o Chondromatosis or villo-nodular synovitis of the knee;

  o Paget’s disease;

  o Ipsilateral coxarthrosis to the known and symptomatic gonarthrosis;

  o Recent knee trauma (<1 month) responsible for pain;

  o Pathologies that could interfere with evaluation (inflammatory and metabolic arthropathy, rheumatoid arthritis, lower limb radiculalgia, arteritis,…).

  o Joint prosthesis (any site)

  o Flare affecting another joint

• Related to anterior and associated treatments:

  o Corticosteroid infiltration received to any joint in the month prior enrollment;

  o Infiltration of hyaluronic acid in the evaluated knee within 6 months before enrollment;

  o Taking NSAIDs or analgesics in the last 48 hours prior to inclusion;

  o No changes in their slow-acting anti-OA drugs and anti-OA dietary supplements over the last 6 months (e.g. chondroitin sulfate, diacerein, avocado soybean unsaponifiables, oxaceprol, copper, glucosamine , anti-OA herbal therapy and homeopathy, …);

  o Taking coumarin anticoagulants and heparins;

  o General corticosteroid;

  o Contraindication to paracetamol.

• About the product:

  o Contraindication to the product (Flexofytol)

• Related to associated pathologies:

  o Serious associated diseases (severe liver failure, renal failure, uncontrolled cardiovascular diseases, …).

• Regarding the patients:

  o Pregnant or lactating women;

  o Premenopausal women not using a contraceptive method;

  o Patient unable to write;

  o Patient who participated in a clinical research in the previous 3 months;

  o Legally responsible adults.