Study of the Plaquenil® efficacy on the endothelial dysfunction and its vascular consequences during the antiphospholipid syndrom

Phase 1

• Conditions: MedDRA version: 18.0Level: PTClassification code 10002817Term: Antiphospholipid syndromeSystem Organ Class: 10005329 - Blood and lymphatic system disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]; Patients must meet the classification criteria for arterial antiphospholipids syndrom. They must have had a confirmed episode of arterial thrombosis and the presence of 2 tests performed at 12 weeks apart of anti-cardiolipin (IgG or IgM ),and anti-B2GP1 (IgG or IgM ), or circulating anticoagulants.

• Registration Number: EUCTR2015-002182-38-FR
• Lead Sponsor: CHU - Hôpitaux de Rouen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-08-05
• Last Update Posted: 11 January 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

-Patients > 18 years old
-Patients must meet the classification criteria for arterial antiphospholipid syndrom. They must have had a confirmed episode of arterial thrombosis and the presence of 2 tests performed at 12 weeks apart of anti-cardiolipin (IgG or IgM ),and anti-B2GP1 (IgG or IgM ), or circulating anticoagulants.
-Patients must be clinically stable (NB : all of stages severity disease will be accepted)
-Patients with medical insurance
-Having read and understood the information letter and signed the consent form
-For women of childbearing age, they needs to take a effective contraception since 1 month (progestin or intrauterin device or tubal ligation) with a negative pregnancy test. (NB: Will be considered postmenopausal women with amenorrhea for more than 2 years)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

- Treatment with hydroxychloroquine (Plaquenil®) already established or stopped for less than 3 months
-Contraindications to Plaquenil® (retinopathy) and sensitivity to chloroquine or hydroxychloroquine or any of the other constituents of Plaquenil®
-Patients presenting a non-arterial or secondary antiphospholipid syndrome
-Symptomatic atherosclerotic disease: Myocardial infarction, angina, coronary revascularization, stroke or transient constituted, arteritis obliterans of lower limbs.
-Heart failure and / or significant valvulopathy.
-Secondary arterial hypertension.
-Severe hypertension (DBP = 110 mm Hg and / or SBP = 180 mm Hg)
-Atrial fibrillation.
-BMI > 35 kg / m2.
-Diabetes diagnosed since more than 3 months.
-Severe chronic renal impairment (creatinine clearance <30 ml / min according to the Cockroft formula).
-Patients with ophthalmic conditions defined by ophthalmologists which oppose the treatment by hydroxychloroquine
-Introduction of any treatment with platelet aggregation inhibitor or anti-inflammatory non-steroid within 7 days preceding the study
-Allergy to lactose
- Contraindications to trinitrine
-Pregnant or breastfeeding women or absence of contraception used
-Person deprived of liberty by an administrative or judicial decision or person placed under judicial protection (guardianship, trusteeship)
- Patients participating in another trial or participated in another trial during the last month

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The main objective is to assess the effect of Plaquenil® on endothelial function, comparatively to a control group, in a population of patient suffering of primary arterial antiphospholipid syndrome;Secondary Objective: 1. Evaluating the effect of Plaquenil® on endothelial glycocalyx<br>2. Evaluating the effect of Plaquenil® on the inflammatory profile<br>3. Evaluating the effect of Plaquenil® on the oxydative stress level<br>4. Evaluating the effect of Plaquenil® on the via tissue factor<br>5. HCQ assay<br>;Primary end point(s): Measuring the variation of the endothelium-dependent dilatation of the brachial artery between baseline and after 6 months of treatment;Timepoint(s) of evaluation of this end point: - inclusion day , 3 and 6 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Measuring the thickness of the endothelial glycocalyx<br>Assays soluble compounds of the glycocalyx<br>Evaluation of oxidative stress <br>Evaluation of the inflammatory component <br>Determination of plasma tissue factor<br>Assay of hydroxychloroquine<br>;Timepoint(s) of evaluation of this end point: - inclusion day 3 and 6 months