Preventive Effect of Clopidogrel on the Systemic Sclerosis Development Risk

In this study, platelet activation is targeted as it could play a key role in the pathogenesis of SSc. It has been shown in several publications that platelets are activated in SSc with a correlation between the level of activation and disease activity. Secondary to this activation, soluble and membrane effectors were increased, and induced vascular damages and fibrosis. The results obtained in the laboratory (CNRS UMR-5164) directly involved platelets in this mechanism by inducing the thymic stromal lymphopoietin (TSLP) production by endothelial cells and by showing the pro-fibrotic effect of TSLP. In vivo data in SSc murine model recently obtained, confirmed the preventive role on fibrosis of clopidogrel. The early control of this platelet activation could prevent the course of events leading to SSc.

The therapeutic strategy assessed in this study will be the oral administration of clopidogrel (75 mg per day) during two years to subjects presenting an association of specific dysimmunity and Raynaud phenomenon (RP). The administration of clopidogrel will be double-blinded versus placebo.

Subjects will be included and treated during a 2-year period and will be followed for a period of 36 months after treatment, i.e. a total of 60 months. The follow-up will be every six months mainly comprising clinical examination, patient reported outcomes and blood sampling.

• Frequency of occurrence of cutaneous fibrosis (sclerodactyly or other affected area) clinically assessed by at least 2 independent investigators in the two randomization groups [Срок оценки: 60 months after baseline (Day 0)]
• Mean of modified Rodnan skin score (which varies between 0 and 51, with higher values mean higher disease severity) in the two randomization groups. [Срок оценки: 60 months after baseline (Day 0)]
• Mean of Cochin hand function scale (which varies between 0 and 90, with higher values mean higher disease severity) in the two randomization groups. [Срок оценки: 60 months after baseline (Day 0)]
• Proportion of sex ratio at inclusion in the two randomization groups. [Срок оценки: At baseline (Day 0)]
• Mean age at inclusion in the two randomization groups. [Срок оценки: At baseline (Day 0)]
• Proportion of patients exposed to toxic products at inclusion in the two randomization groups. [Срок оценки: At baseline (Day 0)]
• Proportion of patients exposed to toxic products at 5 years in the two randomization groups. [Срок оценки: 60 months after baseline (Day 0)]
• Proportion of patients affected by a limited form of SSc at 5 years in the two randomization groups. [Срок оценки: 60 months after baseline (Day 0)]
• Proportion of patients affected by a diffuse form of SSc at 5 years in the two randomization groups. [Срок оценки: 60 months after baseline (Day 0)]
• Proportion of patients presenting a specific antibody positivity (anti-scl70, anti-centromere) in the two randomization groups at inclusion. [Срок оценки: At baseline (Day 0)]
• Proportion of patients presenting megacapillaries by capillaroscopy at 5 years in the two randomization groups. [Срок оценки: 60 months after baseline (Day 0)]