Hydroxychloroquine Versus Placebo: Impact on Thrombotic Relapse in Primary Antiphospholipid Syndrome
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Number of thrombotic events in each arm after 24 months of treatment
研究概览
简要总结
Antiphospholipid syndrome (APS) combines thrombotic (venous and/or arterial) and/or obstetrical manifestations, along with biological anomalies related to the presence of antiphospholipid antibodies. Despite actual treatment recommended by international guidelines, the relapse rate in APS is high and survival is 65% at 15 years. Hydroxychloroquine has demonstrated its efficacy and benefits in the treatment of Systemic Lupus Erythematosus, but there is no current consensus concerning the efficacy of this treatment in the secondary prevention of thrombotic events in primary APS, even though several in vitro experimental and animal model data, along with several clinical studies have suggested a beneficial effect of this drug in this indication. Considering the prevalence of primary APS in the general population and of the number of clinical events observed in patients with primary APS and receiving conventional treatment with vitamin K anticoagulants (VKA), the consortium expects a minimum clinically relevant difference of 70%. Considering a prevalence of thrombotic events for the entire studied primary APS population of 10% at 2 years, the consortium expects a 70% decrease in thrombotic events under Hydroxychloroquine treatment administered in addition to VKA treatment in primary APS, i.e. a 3% prevalence in the Hydroxychloroquine group at 2 years. The consortium proposes a drug trial, phase III, national multicentric, comparative, randomized, superiority, double-blind, controlled with 2 compared groups (Hydroxychloroquine versus placebo) study. The enrolment period will be 24 months.
The main aim of this trial is to comparatively assess at 24 months the number of new thrombotic events (venous and arterial) in primary antiphospholipid syndrome in patients treated with VKA plus Hydroxychloroquine versus VKA plus placebo, in a multicentre, prospective randomized, double-blind, versus placebo study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >18 years
- •Presence of a primary antiphospholipid syndrome with previous venous/arterial thrombosis and which needs a treatment with VKA
- •Patients with a signed commitment
排除标准
- •Secondary APS
- •Ocular diseases :
- •retinal disease contraindicating the prescription of hydroxychloroquine
- •monophtalmic
- •Past history of intolerance or allergy to hydroxychloroquine
- •Known deficit in G6PDase
- •Hemolytic anemia
- •Porphyria
- •Chronic hepatic disease
- •Severe renal failure (creatinin clearence <30ml/min)
- •Chronic alcoholism
- •Patient with QT interval >440 ms on the ECG
- •Concomitant treatment with drugs raising the QT interval
- •Pregnant or breastfeeding women
- •Women refusing an effective contraception
- •Active cancer or malignant hemopathy
- •Psychiatric disease unabling the compliance to treatment
- •Unaffiliated person or not beneficiary of a social security system
- •Concomitant participation at a biomedical trial able to interfere with the actual trial
研究组 & 干预措施
Hydroxychloroquine
All patients randomised in this arm will receive hydroxychloroquine with their usual treatment, which is antivitamin K anticoagulants
干预措施: Hydroxychloroquine (Drug)
Placebo
All patients randomised in this arm will receive a placebo with their usual treatment, which is antivitamin K anticoagulants
干预措施: Placebo (Drug)
结局指标
主要结局
Number of thrombotic events in each arm after 24 months of treatment
时间窗: 24 month
The number of thrombotic events will be compared in the two arms of the study. The events which will be considered are deep venous thrombosis, superficial venous thrombosis, lung embolism, stroke, myocardial infarction as assessed by at least one diagnostic tests such as: doppler echography, lung scintigraphy, lung CT scan, cerebral CT scan, cerebral MRI, myocardial scintigraphy, coronarography.
次要结局
- Number of participants with treatment-related adverse events as assessed by CTCAE(24 month)
- Number of hospitalizations days related to thrombotic event(24 month)
- Number of work incapacity days related to thrombotic event(24 month)
- The specific biological markers of thrombosis in APS such as type and number of antiphospholipid antibodies, complement, antinuclear antibodies, thrombocytosis(24 month)
- Assess compliance to VKA(24 month)
- Assess Assess compliance to HCQ(24 month)
- The vascular arterial rigidity measured by doppler echography(24 month)