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

Depression Clinical Trial

— ANDROS  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02463110
• Other study ID #: P110155
• Status: Terminated
• Phase: Phase 4
• First received: May 19, 2015
• Last updated: May 2, 2016
• Start date: July 2015
• Est. completion date: February 2016

Study information

• Verified date: May 2016
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Depression
• Depressive Disorder
• Myocardial Infarction
• Myocardial Ischemia

Intervention

Drug:
• Sertraline
Sertraline one capsule (50mg per day), which can be increased up to 200mg per day (maximum dose) for 6 months.
• No treatment

• Placebo

Locations

Country	Name	City	State
France	ACTION Group - Pitié-Salpêtrière University Hospital (APHP)	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	ACTION Group – www.action-cœur.org

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	0 day, 1 day, 6 weeks, 24 weeks, 28 weeks	Yes
Secondary	Time dependent pattern of changes in platelet activation	Maximal platelet aggregation (ADP, Arachidonic Acid, Collagen), markers of platelet activation (betaTG, CD40s)	0 day, 1 day, 6 weeks, 24 weeks, 28 weeks	Yes
Secondary	Time dependent pattern of changes in inflammation markers	Dosage of inflammation markers (IL-6, CRP, Fg, myeloperoxydase)	0 day, 1 day, 6 weeks, 24 weeks, 28 weeks	Yes
Secondary	Time dependent changes in Depression	Beck Depression Inventory (BDI)	0 day, 1 day, 6 weeks, 24 weeks, 28 weeks	No
Secondary	Time dependent changes in Tobacco addiction	Fargenström test	0 day, 1 day, 6 weeks, 24 weeks, 28 weeks	No
Secondary	Time dependent changes in Bleeding risk	Dosage of hemoglobin, hematocrit and follow-up of hemorrhage	0 day, 1 day, 6 weeks, 24 weeks, 28 weeks	Yes