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

May 2, 2016 updated by: Assistance Publique - Hôpitaux de Paris

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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)

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75013
        • ACTION Group - Pitié-Salpêtrière University Hospital (APHP)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / 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 Names:
  • Placebo one capsule, which can be increased up to 4 capsules per day (maximum dose) for 6 months.
OTHER: 3: Control
ACS, no depression, no treatment
Drug: No treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
0 day, 1 day, 6 weeks, 24 weeks, 28 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
0 day, 1 day, 6 weeks, 24 weeks, 28 weeks
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)
0 day, 1 day, 6 weeks, 24 weeks, 28 weeks
Time dependent changes in Depression
Time Frame: 0 day, 1 day, 6 weeks, 24 weeks, 28 weeks
Beck Depression Inventory (BDI)
0 day, 1 day, 6 weeks, 24 weeks, 28 weeks
Time dependent changes in Tobacco addiction
Time Frame: 0 day, 1 day, 6 weeks, 24 weeks, 28 weeks
Fargenström test
0 day, 1 day, 6 weeks, 24 weeks, 28 weeks
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
0 day, 1 day, 6 weeks, 24 weeks, 28 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Action Research Group

Investigators

  • Principal Investigator: Johanne SILVAIN, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2015

Primary Completion (ACTUAL)

February 1, 2016

Study Completion (ACTUAL)

February 1, 2016

Study Registration Dates

First Submitted

May 19, 2015

First Submitted That Met QC Criteria

June 1, 2015

First Posted (ESTIMATE)

June 4, 2015

Study Record Updates

Last Update Posted (ESTIMATE)

May 3, 2016

Last Update Submitted That Met QC Criteria

May 2, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P110155

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Depression

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Benin

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe