Clinical trial NCT01937182: The Efficacy of Citalopram Treatment in Acute Stroke
Official title: The Efficacy of Citalopram Treatment in Acute Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stroke, Ischemic
Keywords: Stroke
SSRI (Selective Serotonin Reuptake Inhibitors)
Serotonin
5-HT (5-Hydroxytryptamine)
Neuroprotection
MRI (Magnetic Resonance Imaging)
Platelet
CT (computerized tomography)
Post Stroke Depression
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Danish Council for Independent Research
name: The Danish Regions Medicine Foundation
First posted: 2013-09-09
Enrollment: 642
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Vascular death, Transient Ischemic Attack (TIA)/stroke and myocardial infarction (combined)
timeFrame: 6 months
measure: Functional status at 6-months
timeFrame: 6 months
Secondary outcomes:
measure: Vascular death
timeFrame: 6 months
measure: Death of any cause
timeFrame: 6 months
measure: TIA/stroke
timeFrame: 6 months
measure: Bleeding
timeFrame: 6 months
measure: Myocardial infarction
timeFrame: 6 months
measure: Disability/dependence
timeFrame: 6 months
measure: Physical activity
timeFrame: 6 months
measure: Cognitive and organic cerebral impairment
timeFrame: 6 months
measure: Fatigue
timeFrame: 6 months
measure: Post-stroke depression
timeFrame: 6 months
measure: Pathological Crying
timeFrame: 6 months
measure: Lesion size
timeFrame: 6 months
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital, Department of Neurology
city: Aarhus
country: Denmark
facility: Aarhus University Hospital, Department of Neurology
city: Glostrup
country: Denmark
facility: Glostrup University Hospital, Department of Neurology
Study officials:
affiliation: Aarhus University Hospital
name: Grethe Andersen, DSMc
role: STUDY_CHAIR
affiliation: Aarhus University Hospital
name: Kristian L Kraglund, M.D.
role: STUDY_DIRECTOR
affiliation: Aalborg University Hospital
name: Boris Modrau, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Glostrup University Hospital
name: Helle Iversen, DSMc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Bonaventura A, Liberale L, Vecchie 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):1967. doi: 10.3390/ijms17121967.
citation: 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.
citation: Adelborg K, Sundboll J, Videbech P, Grove EL. The Risk of Thromboembolism in Users of Antidepressants and Antipsychotics. Adv Exp Med Biol. 2017;906:351-361. doi: 10.1007/5584_2016_125.
citation: Kraglund KL, Mortensen JK, Damsbo AG, Modrau B, Simonsen SA, Iversen HK, Madsen M, Grove EL, Johnsen SP, Andersen G. Neuroregeneration and Vascular Protection by Citalopram in Acute Ischemic Stroke (TALOS). Stroke. 2018 Nov;49(11):2568-2576. doi: 10.1161/STROKEAHA.117.020067.