Disease modifying activity of celecoxib on articular cartilage in osteoarthritis.

The objective of the study is to evaluate, in patients with end stage knee osteoarthritis, the in vivo disease (tissue structure) modifying activity of celecoxib, as a selective COX-2 inhibitor, in addition to its inflammation regulatory properties, compared to naproxen as a conventional non-selective NSAID.

This is a blind randomized controlled study.
Patients with knee osteoarthritis, who are eligible for and on the waiting list for total knee replacement surgery are asked to participate. Patients will be assigned to one of the four groups:

One group receives no treatment for 4 weeks, the second group receives 2x daily 200 mg celecoxib for 4 weeks until surgery, the third group receives 2 x daily 200 mg celecoxib for 4 weeks until 3 days before the surgery and the fourth group receives 3 x daily 250 mg naproxen for 4 weeks until 3 days before the surgery. Each group will consist of 43 patients.

Before trial medication starts and at the day of surgery a sample of blood and urine will be taken for biomarker analysis. In addition a WOMAC questionnaire and VAS pain will be evaluated at these timepoints. The knee replacement surgery will take place as scheduled. Cartilage and synovial tissue that are removed as standard procedure during replacement surgery will be used for analyses to evaluate the disease modifying activity in the four groups.

Celecoxib, as a selective COX-2 inhibitor, has in vivo disease modifying activity in addition to its inflammation regulatory properties, in comparison to naproxen as a conventional non-selective NSAID.

First visit: at least 5 weeks before surgery.

Second visit: day of surgery.

a. 4 weeks no treatment;

b. 4 weeks 2x daily 200 mg celecoxib/Celebrex until the surgery;

c. 4 weeks 2x daily 200 mg celecoxib/Celebrex until 3 days before surgery;

d. 4 weeks 3x daily 250 mg.
Naproxen/Aleve until 3 days before surgery.