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

NCT ID: NCT02463110

Last Updated: 2016-05-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2016-02-29

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)

Conditions

Depression; Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1: Sertraline

ACS, depression

Group Type: EXPERIMENTAL

Sertraline

Intervention Type: DRUG

Sertraline one capsule (50mg per day), which can be increased up to 200mg per day (maximum dose) for 6 months.

2: Placebo

ACS, depression

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

3: Control

ACS, no depression, no treatment

Group Type: OTHER

No treatment

Intervention Type: DRUG

Interventions

Sertraline

Sertraline one capsule (50mg per day), which can be increased up to 200mg per day (maximum dose) for 6 months.

Intervention Type: DRUG

No treatment

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Placebo one capsule, which can be increased up to 4 capsules per day (maximum dose) for 6 months.

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Action Research Group

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johanne SILVAIN, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

ACTION Group - Pitié-Salpêtrière University Hospital (APHP)

Paris, , France

Countries

France

Other Identifiers

P110155

Identifier Type: -

Identifier Source: org_study_id