Clinical trial NCT02463110: Acute Myocardial Necrosis and Depression: Antiplatelet Effect of Reuptake Inhibition of Serotonin
Official title: Acute Myocardial Necrosis and Depression: Antiplatelet Effect of Reuptake Inhibition of Serotonin: The ANDROS Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Depression
Coronary Artery Disease
Keywords: Acute Coronary Syndrome
Depression
Coronary Artery Disease
Myocardial Infarction
Percutaneous Coronary Intervention
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Action Research Group
First posted: 2015-06-04
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Randomization and initiation of the treatment at the end of the hospitalization for ACS (possibly after reperfusion and stabilization of cardiac medication)

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Time dependent pattern of changes in platelet reactivity under sertraline compared to placebo within a time Frame of 6 months of treatment
timeFrame: 0 day, 1 day, 6 weeks, 24 weeks, 28 weeks
Secondary outcomes:
measure: Time dependent pattern of changes in platelet activation
timeFrame: 0 day, 1 day, 6 weeks, 24 weeks, 28 weeks
measure: Time dependent pattern of changes in inflammation markers
timeFrame: 0 day, 1 day, 6 weeks, 24 weeks, 28 weeks
measure: Time dependent changes in Depression
timeFrame: 0 day, 1 day, 6 weeks, 24 weeks, 28 weeks
measure: Time dependent changes in Tobacco addiction
timeFrame: 0 day, 1 day, 6 weeks, 24 weeks, 28 weeks
measure: Time dependent changes in Bleeding risk
timeFrame: 0 day, 1 day, 6 weeks, 24 weeks, 28 weeks
Other outcomes:
Locations:
city: Paris
country: France
facility: ACTION Group - Pitié-Salpêtrière University Hospital (APHP)
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Johanne SILVAIN, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: