Preventive Effect of Clopidogrel on the Systemic Sclerosis Development Risk (PSSIT)

January 18, 2024 updated by: University Hospital, Bordeaux

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

90

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Bordeaux, France
        • Recruiting
        • CHU de Bordeaux - service de rhumatologie
        • Contact:
        • Contact:
        • Principal Investigator:
          • Marie-Elise TRUCHETET, Prof
        • Sub-Investigator:
          • Joel CONSTANS, Prof
        • Sub-Investigator:
          • Estibaliz LAZARO, Prof
        • Sub-Investigator:
          • Julien SENESCHAL, Prof
        • Sub-Investigator:
          • Pierre DUFFAU, Prof
      • Brest, France
        • Recruiting
        • CHU de Brest - Service de rhumatologie
        • Contact:
        • Principal Investigator:
          • Alain SARAUX, Prof
      • Libourne, France
        • Not yet recruiting
        • CH de Libourne - service de rhumatologie
        • Contact:
        • Principal Investigator:
          • Jean-Philippe VERNHES, MD
      • Mont-de-Marsan, France
        • Recruiting
        • CH de Mont-de-Marsan - service de rhumatologie
        • Contact:
        • Principal Investigator:
          • Marion MIRABEL, MD
      • Montpellier, France
        • Not yet recruiting
        • CHU de Montpellier - service de médecine vasculaire
        • Contact:
        • Principal Investigator:
          • Pierrick HENNETON, MD
      • Paris, France
        • Recruiting
        • AP-HP - Hôpital Cochin - service de médecine interne
        • Contact:
        • Principal Investigator:
          • Benjamin CHAIGNE, MD
      • Pau, France
        • Not yet recruiting
        • CH de Pau - service de médecine interne
        • Contact:
        • Principal Investigator:
          • Xavier DELBREL, MD
      • Toulouse, France
        • Not yet recruiting
        • CHU de Toulouse - service de médecine interne
        • Contact:
        • Principal Investigator:
          • Gregory Pugnet, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Time Frame: 60 months after baseline (Day 0)
60 months after baseline (Day 0)

Secondary Outcome Measures

Outcome Measure
Time Frame
Frequency of occurrence of cutaneous fibrosis (sclerodactyly or other affected area) clinically assessed by at least 2 independent investigators in the two randomization groups
Time Frame: 60 months after baseline (Day 0)
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.
Time Frame: 60 months after baseline (Day 0)
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.
Time Frame: 60 months after baseline (Day 0)
60 months after baseline (Day 0)
Proportion of sex ratio at inclusion in the two randomization groups.
Time Frame: At baseline (Day 0)
At baseline (Day 0)
Mean age at inclusion in the two randomization groups.
Time Frame: At baseline (Day 0)
At baseline (Day 0)
Proportion of patients exposed to toxic products at inclusion in the two randomization groups.
Time Frame: At baseline (Day 0)
At baseline (Day 0)
Proportion of patients exposed to toxic products at 5 years in the two randomization groups.
Time Frame: 60 months after baseline (Day 0)
60 months after baseline (Day 0)
Proportion of patients affected by a limited form of SSc at 5 years in the two randomization groups.
Time Frame: 60 months after baseline (Day 0)
60 months after baseline (Day 0)
Proportion of patients affected by a diffuse form of SSc at 5 years in the two randomization groups.
Time Frame: 60 months after baseline (Day 0)
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.
Time Frame: At baseline (Day 0)
At baseline (Day 0)
Proportion of patients presenting megacapillaries by capillaroscopy at 5 years in the two randomization groups.
Time Frame: 60 months after baseline (Day 0)
60 months after baseline (Day 0)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Bordeaux

Collaborators

Ministry for Health and Solidarity, France

Investigators

  • Principal Investigator: Marie-Elise TRUCHETET, Prof, CHU Bordeaux
  • Study Chair: Linda WITTKOP, MD, University of Bordeaux

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 22, 2022

Primary Completion (Estimated)

June 1, 2029

Study Completion (Estimated)

June 1, 2029

Study Registration Dates

First Submitted

October 4, 2021

First Submitted That Met QC Criteria

October 15, 2021

First Posted (Actual)

October 28, 2021

Study Record Updates

Last Update Posted (Estimated)

January 19, 2024

Last Update Submitted That Met QC Criteria

January 18, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUBX 2017/45

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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