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Acute Myocardial Necrosis and Depression: Antiplatelet Effect of Reuptake Inhibition of Serotonin (ANDROS)

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ClinicalTrials.gov Identifier: NCT02463110
Recruitment Status : Terminated (Investigator's decision)
First Posted : June 4, 2015
Last Update Posted : May 3, 2016
Sponsor:
Collaborator:
Action Research Group
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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.


Condition or disease Intervention/treatment Phase
Depression Coronary Artery Disease Drug: Sertraline Drug: No treatment Drug: Placebo Phase 4

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)


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Acute Myocardial Necrosis and Depression: Antiplatelet Effect of Reuptake Inhibition of Serotonin: The ANDROS Study
Study Start Date : July 2015
Actual Primary Completion Date : February 2016
Actual Study Completion Date : February 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack

Arm Intervention/treatment
Experimental: 1: Sertraline
ACS, depression
Drug: Sertraline
Sertraline one capsule (50mg per day), which can be increased up to 200mg per day (maximum dose) for 6 months.

Placebo Comparator: 2: Placebo
ACS, depression
Drug: Placebo
Other Name: Placebo one capsule, which can be increased up to 4 capsules per day (maximum dose) for 6 months.

3: Control
ACS, no depression, no treatment
Drug: No treatment



Primary Outcome Measures :
  1. Time dependent pattern of changes in platelet reactivity under sertraline compared to placebo within a time Frame of 6 months of treatment [ Time Frame: 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)



Secondary Outcome Measures :
  1. Time dependent pattern of changes in platelet activation [ Time Frame: 0 day, 1 day, 6 weeks, 24 weeks, 28 weeks ]
    Maximal platelet aggregation (ADP, Arachidonic Acid, Collagen), markers of platelet activation (betaTG, CD40s)

  2. Time dependent pattern of changes in inflammation markers [ Time Frame: 0 day, 1 day, 6 weeks, 24 weeks, 28 weeks ]
    Dosage of inflammation markers (IL-6, CRP, Fg, myeloperoxydase)

  3. Time dependent changes in Depression [ Time Frame: 0 day, 1 day, 6 weeks, 24 weeks, 28 weeks ]
    Beck Depression Inventory (BDI)

  4. Time dependent changes in Tobacco addiction [ Time Frame: 0 day, 1 day, 6 weeks, 24 weeks, 28 weeks ]
    Fargenström test

  5. Time dependent changes in Bleeding risk [ Time Frame: 0 day, 1 day, 6 weeks, 24 weeks, 28 weeks ]
    Dosage of hemoglobin, hematocrit and follow-up of hemorrhage



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02463110


Locations
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France
ACTION Group - Pitié-Salpêtrière University Hospital (APHP)
Paris, France, 75013
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Action Research Group
Investigators
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Principal Investigator: Johanne SILVAIN, MD, PhD Assistance Publique - Hôpitaux de Paris

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02463110     History of Changes
Other Study ID Numbers: P110155
First Posted: June 4, 2015    Key Record Dates
Last Update Posted: May 3, 2016
Last Verified: May 2016
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Acute Coronary Syndrome
Depression
Coronary Artery Disease
Myocardial Infarction
Percutaneous Coronary Intervention
Additional relevant MeSH terms:
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Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Myocardial Infarction
Necrosis
Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes
Sertraline
Serotonin
Antidepressive Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Serotonin Receptor Agonists