The Efficacy of Citalopram Treatment in Acute Stroke

Study Overview
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Brief Summary
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We wish to conduct a prospective, randomized, double blind, placebo controlled multi center study of the combined neuroprotective and antithrombotic effects of SSRI treatment after stroke. Hypotheses: SSRI treatment commenced in the acute phase of stroke (day 0-7) protects against new thromboembolic events and leads to better rehabilitation. 600 stroke patients will be randomized in a 1:1 ratio. 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.

Detailed Description
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Design TALOS is an investigator-initiated, national multicenter randomized- and placebo-controlled, double blind trial testing citalopram in acute ischemic stroke. Randomization Eligible patients will be randomized 1:1 to treatment with either citalopram or placebo. Treatment allocation is double-blinded based on computer-generated algorithm via a dedicated website. Patients whose treatment is stopped within 31 days after inclusion will be replaced. Intervention and follow-up Patients randomized to citalopram will receive oral treatment with 20 mg tablets (10 mg if age ≥65 and/or reduced liver function) for 6 months with telephone contact after 2 weeks and 3 months and follow-up visits at 1 and 6 months. If patients develop depression dosage is initially doubled, followed by an additional control to evaluate effect and, if necessary, shifted to open-label antidepressant treatment. After 6 months, treatment will either stop or switch to open-label antidepressants at the discretion of the investigator. Substudy 120 of patients will begin treatment within 12 hours after treatment with recombinant tissue plasminogen activator. These patients will receive a standard acute magnetic resonance imaging (MRI) with additional perfusion and angio sequences. The 24-hour control scan will be done using MRI instead of conventional CT. Data monitoring When 300 patients have been included in the trial, an interim analysis will be performed. The unblinded results of this analysis will be reviewed by an independent data monitoring committee.

Official Title
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The Efficacy of Citalopram Treatment in Acute Stroke

Conditions
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Stroke, Ischemic

Intervention / Treatment
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* Drug: Citalopram
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First ever ischemic stroke Age 18 years or above Exclusion Criteria: Hemorrhagic stroke Dementia or other neurodegenerative disease Antidepressant medical 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 (eGFR below 30 ml/min per 1.73m2) Hyponatremia (S-potassium below 130 mmol/l) Actively bleeding ulcer Fatal stroke or other severe co-morbidity that markedly decreases expected life span Prolonged corrected QT-interval (QTc above 480 ms) Ongoing treatment with drugs known to prolong the QTc interval

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Selective Serotonin Reuptake Inhibitors<br>Intervention Drug: Citalopram | Drug: Citalopram<br>* Citalopram 10-40 mg per day administered orally<br>* Other names: Cipramil®;|
| Placebo Comparator: Placebo<br>Intervention Drug: Placebo | Drug: Placebo<br>* 1/2-2 tablets per day with no intrinsic drug activity<br>* Other names: inactive substance;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular death, Transient Ischemic Attack (TIA)/stroke and myocardial infarction (combined) | Myocardial Infarction: STEMI (ST segment elevation myocardial infarction) and NSTEMI (non-ST segment elevation myocardial infarction) | 6 months | 
| Functional status at 6-months | Functional status at 6-months, measured by the modified Rankin Scale | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular death |  | 6 months | 
| Death of any cause |  | 6 months | 
| TIA/stroke |  | 6 months | 
| Bleeding | Using the Global Utilization Of Streptokinase And Tpa For Occluded Arteries definition for bleeding (GUSTO) | 6 months | 
| Myocardial infarction | STEMI (ST segment elevation myocardial infarction) and NSTEMI (non-ST segment elevation myocardial infarction) | 6 months | 
| Disability/dependence | Using the modified Rankin Scale and the Barthel Index (BI) | 6 months | 
| Physical activity | Using the Physical Activity Scale for the Elderly (PASE) | 6 months | 
| Cognitive and organic cerebral impairment | Using the Mini-Mental State Examination and the Symbol Digit Modalities Test | 6 months | 
| Fatigue | Using the Multidimensional Fatigue Inventory | 6 months | 
| Post-stroke depression | Using the Major Depression Inventory test (MDI), Global depression scale (self and clinician and Hamilton Depression Scale - 6 item (HAM-D6) | 6 months | 
| Pathological Crying | Using the Pathological Crying Scale | 6 months | 
| Lesion size | Using FLAIR positive lesion size on MRI 24 hours after treatment with Alteplase | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, SSRI (Selective Serotonin Reuptake Inhibitors), Serotonin, 5-HT (5-Hydroxytryptamine), Neuroprotection, MRI (Magnetic Resonance Imaging), Platelet, CT (computerized tomography), Post Stroke Depression