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

Primary Purpose

Depression, Coronary Artery Disease

Status
Terminated
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Sertraline
No treatment
Placebo
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Depression focused on measuring Acute Coronary Syndrome, Depression, Coronary Artery Disease, Myocardial Infarction, Percutaneous Coronary Intervention

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • ACTION Group - Pitié-Salpêtrière University Hospital (APHP)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Other

Arm Label

1: Sertraline

2: Placebo

3: Control

Arm Description

ACS, depression

ACS, depression

ACS, no depression, no treatment

Outcomes

Primary Outcome Measures

Time dependent pattern of changes in platelet reactivity under sertraline compared to placebo within a time Frame of 6 months of treatment
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

Time dependent pattern of changes in platelet activation
Maximal platelet aggregation (ADP, Arachidonic Acid, Collagen), markers of platelet activation (betaTG, CD40s)
Time dependent pattern of changes in inflammation markers
Dosage of inflammation markers (IL-6, CRP, Fg, myeloperoxydase)
Time dependent changes in Depression
Beck Depression Inventory (BDI)
Time dependent changes in Tobacco addiction
Fargenström test
Time dependent changes in Bleeding risk
Dosage of hemoglobin, hematocrit and follow-up of hemorrhage

Full Information

First Posted
May 19, 2015
Last Updated
May 2, 2016
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Action Research Group
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1. Study Identification

Unique Protocol Identification Number
NCT02463110
Brief Title
Acute Myocardial Necrosis and Depression: Antiplatelet Effect of Reuptake Inhibition of Serotonin
Acronym
ANDROS
Official Title
Acute Myocardial Necrosis and Depression: Antiplatelet Effect of Reuptake Inhibition of Serotonin: The ANDROS Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Terminated
Why Stopped
Investigator's decision
Study Start Date
July 2015 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
February 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Action Research Group

4. Oversight

Data Monitoring Committee
No

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression, Coronary Artery Disease
Keywords
Acute Coronary Syndrome, Depression, Coronary Artery Disease, Myocardial Infarction, Percutaneous Coronary Intervention

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1: Sertraline
Arm Type
Experimental
Arm Description
ACS, depression
Arm Title
2: Placebo
Arm Type
Placebo Comparator
Arm Description
ACS, depression
Arm Title
3: Control
Arm Type
Other
Arm Description
ACS, no depression, no treatment
Intervention Type
Drug
Intervention Name(s)
Sertraline
Intervention Description
Sertraline one capsule (50mg per day), which can be increased up to 200mg per day (maximum dose) for 6 months.
Intervention Type
Drug
Intervention Name(s)
No treatment
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo one capsule, which can be increased up to 4 capsules per day (maximum dose) for 6 months.
Primary Outcome Measure Information:
Title
Time dependent pattern of changes in platelet reactivity under sertraline compared to placebo within a time Frame of 6 months of treatment
Description
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)
Time Frame
0 day, 1 day, 6 weeks, 24 weeks, 28 weeks
Secondary Outcome Measure Information:
Title
Time dependent pattern of changes in platelet activation
Description
Maximal platelet aggregation (ADP, Arachidonic Acid, Collagen), markers of platelet activation (betaTG, CD40s)
Time Frame
0 day, 1 day, 6 weeks, 24 weeks, 28 weeks
Title
Time dependent pattern of changes in inflammation markers
Description
Dosage of inflammation markers (IL-6, CRP, Fg, myeloperoxydase)
Time Frame
0 day, 1 day, 6 weeks, 24 weeks, 28 weeks
Title
Time dependent changes in Depression
Description
Beck Depression Inventory (BDI)
Time Frame
0 day, 1 day, 6 weeks, 24 weeks, 28 weeks
Title
Time dependent changes in Tobacco addiction
Description
Fargenström test
Time Frame
0 day, 1 day, 6 weeks, 24 weeks, 28 weeks
Title
Time dependent changes in Bleeding risk
Description
Dosage of hemoglobin, hematocrit and follow-up of hemorrhage
Time Frame
0 day, 1 day, 6 weeks, 24 weeks, 28 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johanne SILVAIN, MD, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
ACTION Group - Pitié-Salpêtrière University Hospital (APHP)
City
Paris
ZIP/Postal Code
75013
Country
France

12. IPD Sharing Statement

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

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