E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
Les patients devront répondre aux critères de classification pour le SAPL artériel primaire. Ils devront avoir eu un épisode de thrombose artérielle confirmée ainsi que la présence sur 2 tests effectués à 12 semaines d’intervalle d’anticorps anticardiolipine IgG ou IgM, anti B2GP1 IgG ou IgM à titres significatifs ou un anticoagulant circulant. |
|
E.1.1.1 | Medical condition in easily understood language |
Antiphospholipid syndrome |
Syndrome des antiphospholipides |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002817 |
E.1.2 | Term | Antiphospholipid syndrome |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
Evaluer l'effet du Plaquenil® sur la fonction endothéliale vasomotrice chez des patients atteints de SAPL primaire artériel comparativement à un groupe contrôle |
|
E.2.2 | Secondary objectives of the trial |
1. Evaluating the effect of Plaquenil® on endothelial glycocalyx 2. Evaluating the effect of Plaquenil® on the inflammatory profile 3. Evaluating the effect of Plaquenil® on the oxydative stress level 4. Evaluating the effect of Plaquenil® on the via tissue factor 5. HCQ assay
|
1. Evaluer l’effet du Plaquenil® sur le glycocalyx endothélial 2. Evaluer l’effet du Plaquenil® sur le profil inflammatoire 3. Evaluer l’effet du Plaquenil® sur le niveau de stress oxydant 4. Evaluer l’effet du Plaquenil® sur un paramètre d’hémostase : le facteur tissulaire 5. Doser l’hydroxychloroquinémie |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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)
|
• Patient > 18 ans • SAPL artériel primaire (les patients devront répondre aux critères de classification pour le SAPL artériel : antécédent d’un épisode de thrombose artérielle confirmée ainsi que la présence sur 2 tests effectués à 12 semaines d’intervalle d’anticorps anticardiolipine IgG ou IgM, anti B2GP1 IgG ou IgM à titres significatifs ou un anticoagulant circulant). • Patient devant être stable cliniquement (NB : tous les stades de gravité de la maladie seront acceptés) • Patient affilié à un régime de Sécurité Sociale • Patient ayant lu et compris la lettre d’information et signé le formulaire de consentement • Pour les femmes en âge de procréer, prise d’une contraception efficace depuis 1 mois (progestative ou dispositif intra-utérin ou ligature des trompes) avec un test de grossesse négatif. (NB : seront considérées comme ménopausées les femmes présentant une aménorrhée depuis plus de 2 ans)
|
|
E.4 | Principal 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
|
• Traitement par hydroxychloroquine (Plaquenil®) déjà instauré ou arrêté depuis moins de 3 mois • Contre-indications au Plaquenil® (rétinopathies) et hypersensibilité à la chloroquine ou à l'hydroxychloroquine ou à l'un des autres constituants du Plaquenil® • Patients porteurs d'un SAPL non artériel, ou secondaire. • Maladie athéromateuse symptomatique: Infarctus du myocarde, angor, revascularisation coronarienne, accident vasculaire cérébral constitué ou transitoire, artérite oblitérante des membres inférieurs. • Insuffisance cardiaque et/ou valvulopathie significative. • Hypertension artérielle secondaire. • Hypertension artérielle sévère (PAD ≥ 110 mm Hg et/ou PAS ≥ 180 mm hg • Diabète diagnostiqué depuis plus de 3 mois. • Insuffisance rénale chronique sévère (clairance de la créatinine < 30 ml/min selon la formule de Cockroft). • Fibrillation auriculaire. • IMC >35 kg/m2. • Femmes enceintes ou allaitantes ou absence de contraception avérée • Contre-indication ophtalmologique à la mise sous Plaquenil définie par les ophtalmologistes. • Contre-indication à la trinitrine • Allergie au lactose • Personne privée de liberté par une décision administrative ou judiciaire ou personne placée sous sauvegarde de justice (tutelle ou curatelle) • Patient participant à un autre essai ou ayant participé à un autre essai médicamenteux dans le mois précédent
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Measuring the variation of the endothelium-dependent dilatation of the brachial artery between baseline and after 6 months of treatment |
Mesure de la variation de la dilatation endothélium-dépendante de l'artère humérale (FMD) entre l'inclusion et après 6 mois de traitement. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
- inclusion day , 3 and 6 months |
- Inclusion, 3 mois et 6 mois |
|
E.5.2 | Secondary end point(s) |
Measuring the thickness of the endothelial glycocalyx Assays soluble compounds of the glycocalyx Evaluation of oxidative stress Evaluation of the inflammatory component Determination of plasma tissue factor Assay of hydroxychloroquine
|
Mesure de l’épaisseur du glycocalyx endothélial et dosages des composés solubles du glycocalyx; Evaluation du stress oxydant (dosage des nitrites plasmatiques et des TBARS (acides thio-barbituriques)) ; Evaluation de la composante inflammatoire (dosage du TNFα) ; mesure du facteur tissulaire plasmatique ; dosage de l’hydroxychloroquine. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- inclusion day 3 and 6 months |
- Inclusion, 3 mois et 6 mois |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
LVLS |
Dernière visite du dernier patient |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | |