Acute Myocardial Necrosis and Depression: Antiplatelet Effect of Reuptake Inhibition of Serotonin: The ANDROS Study
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Time dependent pattern of changes in platelet reactivity under sertraline compared to placebo within a time Frame of 6 months of treatment
研究概览
简要总结
Primary purpose:
To evaluate the evolution in time of the antiaggregant platelet effect of sertraline (SSRI) compared to placebo in depressive patients with ACS (Acute Coronary Syndrome) and treated as recommended by a double antiplatelet therapy, aspirin and clopidogrel.
Hypothesis:
The benefits of SSRIs observed in depressive patients with ACS are related to an antiplatelet effect.
详细描述
Rational:
40% of patients hospitalized for acute coronary syndrome (ACS) present depressive symptoms. The increase in cardiovascular morbidity and mortality at 6 months (hazard ratio = 3.5) could partly be explained by an alteration of the platelet parameters in patients with depression.
Sertraline is a potent inhibitor of the selective serotonin reuptake (SSRI). At the platelet level, it decreases the secretion induced by collagen and causes the inhibition of serotonin reuptake and platelet activation, wider than the simple anti-serotonergic effect. Its efficacy on depression of patients with ACS has been demonstrated (-20% of ischemic events at 24 weeks vs placebo), partly independent of the correction of depressive symptoms, and with a wide safety action. Antiplatelet, anti-inflammatory and endothelial function effects of sertraline are demonstrated in healthy volunteers, in stable patients and in patients with heart failure, but have never been explored in ACS .
Multicenter, randomized, double-blind, controlled trial comparing SSRI and placebo in depressive patients with ACS.
A control (non depressive) ACS group will also do the clinical and laboratory follow-up at the same time (without drug administration), to constitute a reference for platelet parameters and to allow a comparison with the depressive ACS group treated with placebo.
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
- Double (Participant, Investigator)
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
- •Patient Aged 18 years and older
- •Patient Depressive without antidepressant therapy for three months (valid only for the sertraline and placebo groups)
- •Patient With ACS with elevated cardiac enzymes (above the 99th percentile of the upper limit of normal of the laboratory)
- •Patient That assessed depressive symptoms : Test Beck (13 items)
- •Patient Affiliated to a social security scheme (beneficiary or assignee)
- •Patient Having signed a free and informed consent
排除标准
- •Cardiovascular
- •History of serious bleeding (recent hemoglobin fall 5g / dl ( <3 months ), intracranial hemorrhage or hemorrhagic tamponade)
- •Uncontrolled hypertension (SBP > 180 mmHg or DBP > 100 mmHg)
- •Stroke <3 months
- •Treatment with ticagrelor or prasugrel for the duration of the study.
- •Psychiatric
- •Psychosis, bipolar illness
- •Dementia (Mini- Mental State Examination score < 23)
- •Uncontrolled epilepsy
- •Severe depression (score > 15) with suicidal risk identified by a psychiatrist (urgent treatment for depression needed)
- •Patient experienced depression and treated in the last three months or currently receiving treatment
- •Treatment with selective and non-selective monoamine oxidase inhibitors of the group A within 14 days prior to the introduction of sertraline
- •Clinical and Biological
- •Prothrombin time > 1.5 second
- •Platelet rate < 100 000 / mm3
- •Hematocrit rate < 25%
- •Serum creatinine > 4.0 mg / dl
- •Severe hepatic impairment (Child Pugh stage C)
- •Contraindications to sertraline (placebo / sertraline group)
- •Hypersensitivity to the active substance or to any of the excipients (anhydrous lactose, pregelatinized corn starch, sodium laurilsulfate , magnesium stearate)
- •Treatment with pimozide
- •Genetic galactose intolerance, malabsorption of glucose and galactose, lactase deficiency
- •Regulatory
- •Women without effective contraception or pregnant or lactating or desiring pregnancy or within 6 months after randomization
- •Participation in biomedical research on other drugs during the period of participation
- •Patients unable to follow the treatment
研究组 & 干预措施
1: Sertraline
ACS, depression
干预措施: Sertraline (Drug)
2: Placebo
ACS, depression
干预措施: Placebo (Drug)
3: Control
ACS, no depression, no treatment
干预措施: No treatment (Drug)
结局指标
主要结局
Time dependent pattern of changes in platelet reactivity under sertraline compared to placebo within a time Frame of 6 months of treatment
时间窗: 0 day, 1 day, 6 weeks, 24 weeks, 28 weeks
To evaluate the time variation of the level of platelet reactivity (ADP induced residual aggregation) under sertraline compared to placebo within a time Frame of 6 months of treatment. Time Frame: T0 = before starting treatment with sertraline T1 = at discharge from the hospital = J1 after introduction of treatment with sertraline T2 = 6 weeks of treatment with sertraline T3 = 24 weeks of treatment with sertraline = end of treatment with sertraline T4 = 4 weeks after the end of treatment with sertraline (biological and psychiatric rebound)
次要结局
- Time dependent pattern of changes in platelet activation(0 day, 1 day, 6 weeks, 24 weeks, 28 weeks)
- Time dependent pattern of changes in inflammation markers(0 day, 1 day, 6 weeks, 24 weeks, 28 weeks)
- Time dependent changes in Depression(0 day, 1 day, 6 weeks, 24 weeks, 28 weeks)
- Time dependent changes in Tobacco addiction(0 day, 1 day, 6 weeks, 24 weeks, 28 weeks)
- Time dependent changes in Bleeding risk(0 day, 1 day, 6 weeks, 24 weeks, 28 weeks)