The Efficacy of Citalopram Treatment in Acute Stroke

Condition(s) targeted: Stroke

Intervention: Citalopram (Drug); Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of Aarhus

Official(s) and/or principal investigator(s):
Grethe Andersen, DSMc, Study Chair, Affiliation: Aarhus University Hospital
Kristian L Kraglund, M.D., Study Director, Affiliation: Aarhus University Hospital
Boris Modrau, M.D., Principal Investigator, Affiliation: Aalborg Universitetshospital
Helle Iversen, DSMc, Principal Investigator, Affiliation: Glostrup University Hospital

Overall contact:
Kristian L Kraglund, M.D., Phone: +4520739438, Email: kriskrag@rm.dk

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.

Official title: The Efficacy of Citalopram Treatment in Acute Stroke

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Vascular death, Transient Ischemic Attack (TIA)/stroke and myocardial infarction (combined)

Functional status at 6-months

Secondary outcome:

Vascular death

Death of any cause

TIA/stroke

Bleeding

Myocardial infarction

Disability/dependence

Physical activity

Cognitive and organic cerebral impairment

Fatigue

Post-stroke depression

Pathological Crying

Lesion size

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

- 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

Kristian L Kraglund, M.D., Phone: +4520739438, Email: kriskrag@rm.dk

Aalborg University Hospital, Department of Neurology, Aalborg 9100, Denmark; Recruiting
Boris Modrau, M.D., Phone: +45 98165927, Email: boris.modrau@rn.dk
Boris Modrau, M.D., Principal Investigator

Aarhus University Hospital, Department of Neurology, Aarhus 8000, Denmark; Recruiting
Kristian L Kraglund, M.D., Phone: +45 20739438, Email: kriskrag@rm.dk
Grethe Andersen, DSMc, Phone: +45 78463294, Email: greander@rm.dk
Kristian L Kraglund, M.D., Sub-Investigator
Grethe Andersen, DSMc, Principal Investigator
Janne K Mortensen, M.D., Sub-Investigator

Glostrup University Hospital, Department of Neurology, Glostrup 2600, Denmark; Recruiting
Helle Iversen, DSMc, Phone: +45 38633400, Email: heiv@regionh.dk
Helle Iversen, DSMc, Principal Investigator
Sofie A Simonsen, M.D., Sub-Investigator

Starting date: September 2013
Last updated: December 10, 2014