Preventive Effect of Clopidogrel on the Systemic Sclerosis Development Risk

Systemic Sclerosis Clinical Trial

— PSSIT  

Official title:

Phase II/III Double-blind Randomized Placebo-controlled Trial Assessing the Preventive Effect of Clopidogrel on the Systemic Sclerosis Development Risk in Subjects With Specific Dysimmunity and Raynaud Phenomenon

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05098704
• Other study ID #: CHUBX 2017/45
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: June 22, 2022
• Est. completion date: June 2030

Study information

• Verified date: May 2024
• Source: University Hospital, Bordeaux
• Contact: Marie-Elise TRUCHETET, Prof
• Phone: 05.56.79.55.56
• Email: marie-elise.truchetet[@]chu-bordeaux.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Systemic sclerosis (SSc) is a severe autoimmune disease associating dysimmunity, vasculopathy and fibrosis. No curative treatment is available. Pre-clinical abnormalities can be found such as specific autoantibodies. The association of Raynaud phenomenon and SSc-specific anti-nuclear antibodies is the hallmark of pre-scleroderma subjects, among who around 47% declare a complete disease after five years. The aim of this study is to assess in this particular population the preventive effect of an anti-platelet treatment.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: June 2030
• Est. primary completion date: June 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Patient over 18 years old, and less than 85 years old.

• Patient with positive AAN (AAN = 1/160) with the following specificity: anti-Scl70 or anti-centromere or anti-RNApolIII, or any other auto-antibodies related to systemic sclerosis

• Patient with RP reported by the subject and confirmed by the physician.

• Patient affiliated to a health insurance system.

• Patient who accepts to participate to the study and signs an inform consent form.

Exclusion Criteria:

• Patient with an SSc diagnosis according to ACR/EULAR 2013 criteria.

• Patient with skin fibrosis at screening.

• Patient with antiplatelet treatment at screening.

• Patient with contraindications to clopidogrel.

• Patient treated by immunosuppressive agent at screening.

• Patient treated by anticoagulants at screening

• Pregnant or breastfeeding women.

• Women of childbearing age refusing effective contraception method during the study treatment (24 months).

• Incompetent adults (i.e. Individuals under the protection of a conservator)

Related Conditions & MeSH terms

• Scleroderma
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis

Intervention

Drug:
• clopidogrel treatment
75 mg daily during 24 months
• Placebo
75 mg daily during 24 months

Locations

Country	Name	City	State
France	CHU de Bordeaux - service de rhumatologie	Bordeaux
France	CHU de Brest - service de rhumatologie	Brest
France	CH de Libourne - service de rhumatologie	Libourne
France	CH de Mont-de-Marsan - service de rhumatologie	Mont-de-Marsan
France	CHU de Montpellier - service de médecine vasculaire	Montpellier
France	AP-HP - Hôpital Cochin - service de médecine interne	Paris
France	CH de Pau - service de médecine interne	Pau
France	CHU de Toulouse - service de médecine interne	Toulouse

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Bordeaux	Ministry for Health and Solidarity, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of occurrence of SSc at 5 years according to American College of Rheumatology (ACR) / European League Against Rhumatism (EULAR) 2013 criteria in the two randomization groups		60 months after baseline (Day 0)
Secondary	Frequency of occurrence of cutaneous fibrosis (sclerodactyly or other affected area) clinically assessed by at least 2 independent investigators in the two randomization groups		60 months after baseline (Day 0)
Secondary	Mean of modified Rodnan skin score (which varies between 0 and 51, with higher values mean higher disease severity) in the two randomization groups.		60 months after baseline (Day 0)
Secondary	Mean of Cochin hand function scale (which varies between 0 and 90, with higher values mean higher disease severity) in the two randomization groups.		60 months after baseline (Day 0)
Secondary	Proportion of sex ratio at inclusion in the two randomization groups.		At baseline (Day 0)
Secondary	Mean age at inclusion in the two randomization groups.		At baseline (Day 0)
Secondary	Proportion of patients exposed to toxic products at inclusion in the two randomization groups.		At baseline (Day 0)
Secondary	Proportion of patients exposed to toxic products at 5 years in the two randomization groups.		60 months after baseline (Day 0)
Secondary	Proportion of patients affected by a limited form of SSc at 5 years in the two randomization groups.		60 months after baseline (Day 0)
Secondary	Proportion of patients affected by a diffuse form of SSc at 5 years in the two randomization groups.		60 months after baseline (Day 0)
Secondary	Proportion of patients presenting a specific antibody positivity (anti-scl70, anti-centromere) in the two randomization groups at inclusion.		At baseline (Day 0)
Secondary	Proportion of patients presenting megacapillaries by capillaroscopy at 5 years in the two randomization groups.		60 months after baseline (Day 0)