Escitalopram Treatment In Acute Stroke (ESTIAS)

Efficacy of Escitalopram Treatment in Acute Stroke and the Role of SERT Genotype in Stroke

Growing international scientific evidence has indicated a positive effect of SSRI treatment (serotonin reuptake inhibitors) after stroke, beyond its antidepressant effect. We wish to conduct a prospective randomised double blind placebo-controlled multicenter study of the combined neuroprotective and antithrombotic effects of SSRI treatment after stroke. Deletion of the SERT (serotonin transporter) gene may influence this treatment effect and may in itself be a risk factor for stroke, an aspect we also wish to explore.

Hypotheses:

1. SSRI treatment commenced in the acute phase of stroke (day 2-5) protects against new thromboembolic events and leads to better rehabilitation.
2. A specific SERT genotype is associated with an increased risk of first ever stroke.
3. A specific SERT genotype is associated with a higher risk of post stroke depression.

600 stroke patients will be randomised to either escitalopram or placebo treatment in a 1:1 ratio and genotyped according to SERT polymorphisms. The treatment and follow up period is 6 months. During these 6 months there will be 2 clinical follow up visits, one telephone control and one visit to evaluate compliance regarding medication. Patients who had an MRI as a part of the routine investigations done upon admission (approximately 300 patients) will have a control MRI after 6 months.

Additionally 400 patients, not eligible for participation i the randomised controlled trial, will be genotyped and answer questionnaires after 1 and 6 months.

Study Overview

• Status: Withdrawn
• Conditions: Stroke
• Intervention / Treatment: Drug: Placebo; Drug: Escitalopram

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Neurology Department, Aalborg Hospital
  • Aarhus, Denmark, 8000
    • Neurology Department, University Hospital of Aarhus
  • Glostrup, Denmark, 2600
    • Neurology Department, Glostrup Hospital

Participation Criteria

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:

• First ever ischemic stroke
• Age 18 years or above

Exclusion Criteria

• Hemorrhagic stroke
• Dementia or other neurodegenerative disease
• Antidepressant treatment within 6 months of admission
• Acute need for antidepressant treatment
• Drug abuse or other conditions that may indicate noncompliant behavior
• Liver failure (increased liver enzyme levels up to or more than 2 times upper limit)
• Renal failure (GFR under 30)
• Hyponatremia (S-potassium below 130 mmol/l)
• Actively bleeding ulcer
• Fatal stroke or other severe co morbidity that markedly decreases expected life span
• Prolonged QT interval (QTc above 500 ms)
• Ongoing treatment with drugs known to prolong the QT interval

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Escitalopram	Drug: Escitalopram; 5 or 10 mg escitalopram tablets administered orally once daily; Other Names: Cipralex; SSRI
PLACEBO_COMPARATOR: Non active drug	Drug: Placebo; Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
New vascular events	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death of any cause		6 months
Myocardial Infarction		6 months
Re-stroke		6 months
Motor function	Fugl-Meyer Motor score is performed	6 months
White Matter lesions	Evaluated on MRI	6 months
Bleeding complications		6 months
Combined vascular death		6 months
Cognitive abilities	SDMT and MMSE tests are performed	6 months

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital
• Investigators: Principal Investigator: Grethe Andersen, Prof. DMSc, University Hospital of Aarhus, Neurology Dept.

Study record dates

Study Registration Dates

• First Submitted: March 20, 2012
• First Submitted That Met QC Criteria: March 20, 2012
• First Posted (ESTIMATE): March 22, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): June 19, 2012
• Last Update Submitted That Met QC Criteria: June 18, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Stroke; RCT; Outcome; SSRI
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Citalopram
• Other Study ID Numbers: 397-2011