A two-year prospective, randomized, double-blind, controlled study assessing the effect of chondroitin 4&6 sulfate (CS) on the structural progression of knee osteoarthritis: STOPP (STudy on osteoarthritis progression prevention)

PURPOSE:

STOPP was designed to evaluate the structure and modifying properties of CS in patients with knee OA by using a highly performing radiographic method (Lyon schuss view).

METHODS:

STOPP is a prospective, multicentre, randomized, parallel groups, double blind, study comparing orally administered chondroitin 4&6 sulfate, 800 mg and placebo over 24 months in patients with knee OA. 600 patients, from both genders, aged 45-80 years with tibio-femoral knee osteoarthritis (pain and radiological signs) were recruited in Europe and North America. A minimal level of pain of 30 mm (VAS) was requested for inclusion. Signal joint was defined as the knee with the most severe joint space narrowing (X-rays). The primary efficacy outcome was the minimal joint space narrowing (JSN) measured over two years, on digitalised X-rays (Lyon schuss view). Secondary efficacy outcomes included pain (VAS, WOMAC, intake of analgesics and NSAIDs). The digitalised X-rays were analysed blindly with respect to treatment and time, at the end of the study, and validated by an automated image analysis (E.V.).

RESULTS:

A total of 622 patients (CS=309; placebo=313) meeting the inclusion criteria were enrolled between the years 2000 and 2002. The study groups were balanced at baseline with respect to demographic and clinical variables, including severity of OA of the signal joint. Ninety-three patients (30.1%) of the CS group and 80 patients (25.6%) of the placebo group dropped out with no significant differences between groups regarding the reasons. Good compliance (> 80 %) was shown in both groups. In the intention-to-treat analysis, patients from the placebo group had a mean (SE) JSN of 0.24 ± 0.03 mm after 2 years, which was significantly prevented in the group treated with CS (0.10 ± 0.03 mm) (p<0.01). The per protocol analysis confirmed the results obtained in the ITT analysis. The interaction time x treatment showed a statistically significant difference in pain VAS and WOMAC (p<0.01) in favour of CS.

CONCLUSIONS:

Chondroitin 4&6 sulfate (CS) is able to significantly reduce the progression of joint space narrowing in patients with knee osteoarthritis compared to placebo. This structure-modifying effect is complemented by a significant difference in the clinical evolution of the disease.