PSSIT: Preventive Effect of Clopidogrel on the Systemic Sclerosis Development Risk

Sponsor

University Hospital, Bordeaux (Other)

Overall Status

Recruiting

CT.gov ID

NCT05098704

Collaborator

Ministry for Health and Solidarity, France (Other)

Enrollment

Locations

Arms

83.3

Anticipated Duration (Months)

12.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Scleroderma Systemic Sclerosis	Drug: clopidogrel treatment Drug: Placebo	Phase 2/Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

placebo-controlled trialplacebo-controlled trial

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 22, 2022

Anticipated Primary Completion Date :

Jun 1, 2029

Anticipated Study Completion Date :

Jun 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: clopidogrel	Drug: clopidogrel treatment 75 mg daily during 24 months
Placebo Comparator: placebo	Drug: Placebo 75 mg daily during 24 months

Arm

Intervention/Treatment

Experimental: clopidogrel

Drug: clopidogrel treatment

75 mg daily during 24 months

Placebo Comparator: placebo

Drug: Placebo

75 mg daily during 24 months

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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)]
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)]
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)]
Proportion of sex ratio at inclusion in the two randomization groups. [At baseline (Day 0)]
Mean age at inclusion in the two randomization groups. [At baseline (Day 0)]
Proportion of patients exposed to toxic products at inclusion in the two randomization groups. [At baseline (Day 0)]
Proportion of patients exposed to toxic products at 5 years in the two randomization groups. [60 months after baseline (Day 0)]
Proportion of patients affected by a limited form of SSc at 5 years in the two randomization groups. [60 months after baseline (Day 0)]
Proportion of patients affected by a diffuse form of SSc at 5 years in the two randomization groups. [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. [At baseline (Day 0)]
Proportion of patients presenting megacapillaries by capillaroscopy at 5 years in the two randomization groups. [60 months after baseline (Day 0)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
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.
Pregnant or breastfeeding women.
Women of childbearing age refusing effective contraception method during the study.
Incompetent adults (i.e. Individuals under the protection of a conservator)

Contacts and Locations

Locations

	Site	City	Country
1	CHU de Bordeaux - service de rhumatologie	Bordeaux	France
2	CHU de Brest - service de rhumatologie	Brest	France
3	CHU de Limoges - Service de médecine interne	Limoges	France
4	CH de Mont-de-Marsan - service de rhumatologie	Mont-de-Marsan	France
5	CHU de Montpellier - service de rhumatologie	Montpellier	France
6	CH de Pau - service de médecine interne	Pau	France
7	CHU de Toulouse - service de médecine interne	Toulouse	France