Efficacy and Safety of Etoricoxib+Diacerein in Osteoarthritis.

Exclusion Criteria

• •1. Patients with allergy or hypersensitivity to the study medications (including the rescue medication) or to any of their excipients.
• •2. Patients with a body mass index ≥ 39.
• •3. Patients with a history of rapidly progressive hip OA.
• •4. Patients with a history of inflammatory joint disease other than OA (e.g., rheumatoid arthritis, lupus erythematosus, psoriatic arthritis, pseudogout, acute gout, joint infections) or seronegative spondyloarthropathy, Paget's disease of the spine, pelvis, or femur, neuropathic disorders, multiple sclerosis, fibromyalgia, spinal cord tumors or infections, or renal osteodystrophy.
• •5. History of arthropathy (osteonecrosis, insufficiency fracture of subchondral bone, rapidly progressive osteoarthritis type 1 or type 2), neuropathic joint arthropathy, hip dislocation, knee dislocation, extensive subchondral cysts, significant bone collapse, significant loss of bone mass, or pathological fractures.
• •6. Scheduled joint replacement surgery to be performed during the study period, or arthroscopic procedures within 6 months prior to study initiation.
• •7. Trauma to the index joint within 30 days prior to the screening visit.
• •8. Use of systemic corticosteroids within 30 days prior to the screening visit or intra-articular corticosteroids in the index joint within 12 weeks prior to the screening visit.
• •9. Concomitant use of medications with laxative effects.
• •10. Continuous oral treatment (at least 90 days) with a SYSADOA medication (chondroitin sulfate, glucosamine sulfate, diacerein, or other) within 3 months before the start of the study.
• •11. Use of monoamine reuptake inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors for pain treatment within 4 weeks prior to the screening visit.
• •12. History of peptic ulcer or gastrointestinal bleeding within 12 months prior to the screening visit and/or medical contraindication for the use of NSAIDs.
• •13. Severe gastrointestinal disorders, including persistent diarrhea (≥3 bowel movements/24 hours).
• •14. Renal insufficiency (serum creatinine ≥1.8 mg/dL or 2+ proteinuria on a test or a glomerular filtration rate \<30 mL/min).
• •15. Liver enzyme levels (ALT, AST, GST) elevated ≥2.5 times the upper limit of normal at the time of screening.
• •16. History or presence of cardiovascular diseases (e.g., second- or third-degree heart block, first-degree heart block with abnormal QRS or bifascicular block, history of uncontrolled arterial hypertension, congestive heart failure classified as NYHA stage II-IV, transient ischemic attack (TIA) or stroke within 12 months prior to the screening visit, or myocardial infarction or acute coronary syndromes or evidence of peripheral vascular insufficiency with claudication within 6 months prior to the screening visit).
• •17. History of other comorbidities that, in the investigator's judgment, could affect the subject's participation in the study, their safety, or the outcome of the study variables.
• •18. Current history of alcoholism and/or drug abuse.
• •19. Current participation in a clinical research study evaluating another investigational drug or having received another investigational product within 30 days prior to the screening visit.
• •20. Women with a positive pregnancy test at the time of screening or who are breastfeeding.