TALOS: The Efficacy of Citalopram Treatment in Acute Stroke
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Selective Serotonin Reuptake Inhibitors Intervention Drug: Citalopram |
Drug: Citalopram
Citalopram 10-40 mg per day administered orally
Other Names:
|
| Placebo Comparator: Placebo Intervention Drug: Placebo |
Drug: Placebo
1/2-2 tablets per day with no intrinsic drug activity
Other Names:
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Outcome Measures
Primary Outcome Measures
- 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
- Vascular death [6 months]
- Death of any cause [6 months]
- TIA/stroke [6 months]
- Bleeding [6 months]
Using the Global Utilization Of Streptokinase And Tpa For Occluded Arteries definition for bleeding (GUSTO)
- Myocardial infarction [6 months]
STEMI (ST segment elevation myocardial infarction) and NSTEMI (non-ST segment elevation myocardial infarction)
- Disability/dependence [6 months]
Using the modified Rankin Scale and the Barthel Index (BI)
- 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
Eligibility Criteria
Criteria
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
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Aalborg University Hospital, Department of Neurology | Aalborg | Denmark | 9100 | |
| 2 | Aarhus University Hospital, Department of Neurology | Aarhus | Denmark | 8000 | |
| 3 | Glostrup University Hospital, Department of Neurology | Glostrup | Denmark | 2600 |
Sponsors and Collaborators
- University of Aarhus
- Danish Council for Independent Research
- The Danish Regions Medicine Foundation
Investigators
- Study Chair: Grethe Andersen, DSMc, Aarhus University Hospital
- Study Director: Kristian L Kraglund, M.D., Aarhus University Hospital
- Principal Investigator: Boris Modrau, M.D., Aalborg University Hospital
- Principal Investigator: Helle Iversen, DSMc, Glostrup University Hospital
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Adelborg K, Sundbøll J, Videbech P, Grove EL. The Risk of Thromboembolism in Users of Antidepressants and Antipsychotics. Adv Exp Med Biol. 2017;906:351-361. Review.
- Bonaventura A, Liberale L, Vecchié A, Casula M, Carbone F, Dallegri F, Montecucco F. Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke. Int J Mol Sci. 2016 Nov 25;17(12). pii: E1967. Review.
- Mortensen JK, Johnsen SP, Larsson H, Andersen G. Early Antidepressant Treatment and All-Cause 30-Day Mortality in Patients with Ischemic Stroke. Cerebrovasc Dis. 2015;40(1-2):81-90. doi: 10.1159/000435819. Epub 2015 Jul 11.
- Siepmann T, Penzlin AI, Kepplinger J, Illigens BM, Weidner K, Reichmann H, Barlinn K. Selective serotonin reuptake inhibitors to improve outcome in acute ischemic stroke: possible mechanisms and clinical evidence. Brain Behav. 2015 Sep 23;5(10):e00373. doi: 10.1002/brb3.373. eCollection 2015 Oct. Review.
- 2013-002253-30