[SOCRATES -Acute Stroke Or Transient IsChaemic Attack TReated With Aspirin or Ticagrelor and Patient OutcomES]

Study Overview
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Brief Summary
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The primary objective of the study is to compare the effect of 90-day treatment with ticagrelor (180 mg [two 90 mg tablets] loading dose on Day 1 followed by 90 mg twice daily maintenance dose for the remainder of the study) vs acetylsalicylic acid (ASA)-aspirin (300 mg [three 100 mg tablets] loading dose on Day 1 followed by 100 mg once daily maintenance dose for the remainder of the study) for the prevention of major vascular events (composite of stroke, myocardial infarction [MI], and death) in patients with acute ischaemic stroke or transient ischaemic attack (TIA).

Official Title
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A Randomised, Double-Blind, Multinational Study to Prevent Major Vascular Events With Ticagrelor Compared to Aspirin (ASA) in Patients With Acute Ischaemic Stroke or TIA.

Conditions
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Acute Ischaemic Stroke, Transient Ischaemic Attack

Intervention / Treatment
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* Drug: ticagrelor
* Drug: Acetylsalicylic acid (ASA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women equal or elder 40 years of age Either acute ischaemic stroke or high-risk TIA as defined here and randomisation occurring within 24 hours after onset of symptoms Key Exclusion Criteria: Planned use of antithrombotic therapy in addition to study medication including antiplatelets (eg, open label ASA, GPIIb/IIIa inhibitors, clopidogrel, ticlopidine, prasugrel, dipyridamole, ozagrel, cilostazol) and anticoagulants (eg, warfarin, oral thrombin and factor Xa inhibitors, bivalirudin, hirudin, argatroban, unfractionated and low molecular weight heparins). - Any history of atrial fibrillation, ventricular aneurysm or suspicion of cardioembolic pathology for TIA or stroke. - Planned carotid, cerebrovascular, or coronary revascularisation that requires halting study medication within 7 days of randomisation. - Receipt of any intravenous or intra-arterial thrombolysis or mechanical thrombectomy within 24 hours prior to randomisation - History of previous symptomatic non-traumatic intracerebral bleed at any time (asymptomatic microbleeds do not qualify), gastrointestinal (GI) bleed within the past 6 months, or major surgery within 30 days.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 130 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ticagrelor<br> | Drug: ticagrelor<br>* ticagrelor, 180 mg (two tablets of 90 mg) loading dose on Day 1 followed by 90 mg twice daily.<br>|
| Active Comparator: Acetylsalicylic acid (ASA)<br> | Drug: Acetylsalicylic acid (ASA)<br>* ASA, 300 mg (three tablets of 100 mg) on Day 1, followed by 100 mg once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Composite of Stroke/MI/Death | Participants with stroke, MI or death. If no event, censoring occures at the minimum of (last date of event assessment, end of treatment date, day 97). | From randomization up to 97 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Ischaemic Stroke | Participants with ischaemic stroke. If no event, censoring occures at the minimum of (last date of event assessment, date of death, end of treatment date, day 97). | From randomization up to 97 days | 
| Net Clinical Outcome | Participants with stroke, MI, death or life-threatening bleeding. If no event, censoring occures at the minimum of (last date of event assessment, end of treatment date, day 97). | From randomization up to 97 days | 
| Number of Participants With Composite of Ischaemic Stroke, MI and CV Death | Participants with ischaemic stroke, MI or CV death. If no event, censoring at the minimum of (last date of event assessment, date of death from non-CV causes, end of treatment date, day 97). | From randomization up to 97 days | 
| Number of Participants With All-Cause Death | Participants with all-cause death. If no event, censoring at the minimum of (last date of event assessment, end of treatment date, day 97). | From randomization up to 97 days | 
| Number of Participants With CV Death | Participants with CV death. If no event, censoring at the minimum of (last date of event assessment, date of death from non-CV causes, end of treatment date, day 97). | From randomization up to 97 days | 
| Number of Participants With MI | Participants with MI. If no event, censoring at the minimum of (last date of event assessment, date of death, end of treatment date, day 97) | From randomization up to 97 days | 
| Number of Participants by Severity of Stroke and Overall Disability | Analysis of severity of stroke and overall disability of patients, using the modified Rankin Score, mRS. Modified Rankin Score: 0 - No symptoms. - No significant disability. Able to carry out all usual activities, despite some symptoms. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. - Moderate disability. Requires some help, but able to walk unassisted. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. - Dead. Disability defined as mRS > 1. Odds ratio and p-value are calculated for ticagrelor versus ASA from a logistic regression model with treatment group, history of stroke and NIHSS (National Institutes of Health Stroke Scale) at baseline as explanatory variables. | From randomization up to 97 days | 
| Number of Participants With Stroke | Participants with stroke. If no event, censoring at the minimum of (last date of event assessment, date of death, end of treatment date, day 97) | From randomization up to 97 days | 
| Number of Participants With Fatal Stroke | Participants with fatal stroke. If no event, censoring at the minimum of (last date of event assessment, date of death from non-CV causes, end of treatment date, day 97). | From randomization up to 97 days | 
| Number of Participants With Disabling Stroke | Participants with disabling stroke. If no event, censoring at the minimum of (last date of event assessment, date of death, end of treatment date, day 97). | From randomization up to 97 days | 
| Change in NIHSS | Change from baseline to end of treatment visit in NIHSS (National Institutes of Health Stroke Scale): 0 No stroke symptoms 1-4 Minor stroke 5-15 Moderate stroke 16-20 Moderate to severe stroke 21-42 Severe stroke. | From randomization up to 97 days | 
| EQ-5D at Visit 1 (Enrolment) | EQ-5D (EuroQol five dimensions questionnaire) index score using the UK tariff. EQ-5D is a self assessment of 5 dimensions: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. For each dimension responders are asked to state their status on a three level ordinal scale; whether they experience no problems (Level 1), some problems (Level 2) or severe problems (Level 3). Health states defined by the 5 dimensions can be converted into a weighted health state index (health state utility) by applying scores from the EQ-5D value sets elicited from general population samples. The higher the index score the better the health state. In this study index scores ran from -0.59 to 1. | Visit 1 (Enrolment) | 
| EQ-5D at Visit 2 (Day 7+-2d) | EQ-5D (EuroQol five dimensions questionnaire) index score using the UK tariff. EQ-5D is a self assessment of 5 dimensions: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. For each dimension responders are asked to state their status on a three level ordinal scale; whether they experience no problems (Level 1), some problems (Level 2) or severe problems (Level 3). Health states defined by the 5 dimensions can be converted into a weighted health state index (health state utility) by applying scores from the EQ-5D value sets elicited from general population samples. The higher the index score the better the health state. In this study index scores ran from -0.59 to 1. | Visit 2 (Day 7+-2d) | 
| EQ-5D (EuroQol Five Dimensions Questionnaire) at End of Treatment Visit | EQ-5D index score using the UK tariff. EQ-5D is a self assessment of 5 dimensions: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. For each dimension responders are asked to state their status on a three level ordinal scale; whether they experience no problems (Level 1), some problems (Level 2) or severe problems (Level 3). Health states defined by the 5 dimensions can be converted into a weighted health state index (health state utility) by applying scores from the EQ-5D value sets elicited from general population samples. The higher the index score the better the health state. In this study index scores ran from -0.59 to 1. | End of treatment visit (Day 90+-7d) | 
| EQ-5D (EuroQol Five Dimensions Questionnaire) at Premature Treatment Discontinuation Visit | EQ-5D index score using the UK tariff. EQ-5D is a self assessment of 5 dimensions: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. For each dimension responders are asked to state their status on a three level ordinal scale; whether they experience no problems (Level 1), some problems (Level 2) or severe problems (Level 3). Health states defined by the 5 dimensions can be converted into a weighted health state index (health state utility) by applying scores from the EQ-5D value sets elicited from general population samples. The higher the index score the better the health state. In this study index scores ran from -0.59 to 1. | Premature treatment discontinuation visit(<15 days after last dose) | 
| Number of Participants With PLATO Major Bleeding Event | Participants with PLATO Major bleeding. If no event, censoring occures at the minimum of (last date of event assessment, date of death, end of treatment date, day 97). PLATO Major bleeding is defined as a bleed that is any one of: Fatal Intracranial (excluding asymptomatic haemorrhagic transformations of ischemic brain infarctions and excluding micro-hemorrhages <10 mm evident only on gradient-echo MRI) Intrapericardial bleed with cardiac tamponade Hypovolaemic shock or severe hypotension due to bleeding and requiring pressors or surgery Significantly disabling (eg. intraocular with permanent vision loss) Clinically overt or apparent bleeding associated with a decrease in Hb of more than 30 g/L (1.9 mmol/L; 0.465 mmol/L) Transfusion of 2 or more units (whole blood or packed red blood cells [PRBCs]) for bleeding. | From randomization up to 97 days | 
| Number of Participants With Premature Discontinuation of Study Drug Due to Any Bleeding Adverse Event | Participants discontinuation of study drug due to any bleeding adverse event. If no event, censoring occures at the minimum of (last date of event assessment, date of death, end of treatment date, day 97). | Time from first dose and up to and including 7 days following the date of last dose of the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute ischaemic stroke., Transient ischaemic attack.