The Efficacy of Citalopram Treatment in Acute Stroke

Phase 2

Completed

• Conditions: Stroke, Ischemic
• Interventions: Drug: Placebo; Drug: Citalopram

• Registration Number: NCT01937182
• Lead Sponsor: University of Aarhus

Brief Summary

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

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.

Study Timeline

• Study Start: 2013-09
• Study First Submitted: 2013-09-03
• Study First Submitted QC: 2013-09-03
• Study First Posted: 2013-09-09
• Status Verified: 2016-12
• Primary Completion: 2016-12-19
• Study Completion: 2016-12-19
• Last Update Submitted: 2017-02-23
• Last Update Posted: 2017-02-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 642

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Intervention Drug: Placebo
Selective Serotonin Reuptake Inhibitors	Citalopram	Intervention Drug: Citalopram

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (3)

Aalborg University Hospital, Department of Neurology; 🇩🇰 Aalborg, Denmark

Aarhus University Hospital, Department of Neurology; 🇩🇰 Aarhus, Denmark

Glostrup University Hospital, Department of Neurology; 🇩🇰 Glostrup, Denmark