Brief Summary
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).
Brief Title
[SOCRATES -Acute Stroke Or Transient IsChaemic Attack TReated With Aspirin or Ticagrelor and Patient OutcomES]
Categories
Completion Date
Completion Date Type
Actual
Conditions
Acute Ischaemic Stroke
Transient Ischaemic Attack
Eligibility Criteria
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.
* 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.
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Keywords
Acute ischaemic stroke.
Transient ischaemic attack.
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
130 Years
Minimum Age
40 Years
NCT Id
NCT01994720
Org Class
Industry
Org Full Name
AstraZeneca
Org Study Id
D5134C00001
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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.
Primary Outcomes
Outcome Description
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).
Outcome Measure
Number of Participants With Composite of Stroke/MI/Death
Outcome Time Frame
From randomization up to 97 days
Secondary Ids
Secondary Id
2012-003895-38
Secondary Outcomes
Outcome Description
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).
Outcome Time Frame
From randomization up to 97 days
Outcome Measure
Number of Participants With Ischaemic Stroke
Outcome Description
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).
Outcome Time Frame
From randomization up to 97 days
Outcome Measure
Net Clinical Outcome
Outcome Description
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).
Outcome Time Frame
From randomization up to 97 days
Outcome Measure
Number of Participants With Composite of Ischaemic Stroke, MI and CV Death
Outcome Description
Participants with all-cause death. If no event, censoring at the minimum of (last date of event assessment, end of treatment date, day 97).
Outcome Time Frame
From randomization up to 97 days
Outcome Measure
Number of Participants With All-Cause Death
Outcome Description
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).
Outcome Time Frame
From randomization up to 97 days
Outcome Measure
Number of Participants With CV Death
Outcome Description
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)
Outcome Time Frame
From randomization up to 97 days
Outcome Measure
Number of Participants With MI
Outcome Description
Analysis of severity of stroke and overall disability of patients, using the modified Rankin Score, mRS.
Modified Rankin Score:
0 - No symptoms.
1. - No significant disability. Able to carry out all usual activities, despite some symptoms.
2. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
3. - Moderate disability. Requires some help, but able to walk unassisted.
4. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
5. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
6. - 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.
Modified Rankin Score:
0 - No symptoms.
1. - No significant disability. Able to carry out all usual activities, despite some symptoms.
2. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
3. - Moderate disability. Requires some help, but able to walk unassisted.
4. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
5. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
6. - 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.
Outcome Time Frame
From randomization up to 97 days
Outcome Measure
Number of Participants by Severity of Stroke and Overall Disability
Outcome Description
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)
Outcome Time Frame
From randomization up to 97 days
Outcome Measure
Number of Participants With Stroke
Outcome Description
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).
Outcome Time Frame
From randomization up to 97 days
Outcome Measure
Number of Participants With Fatal Stroke
Outcome Description
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).
Outcome Time Frame
From randomization up to 97 days
Outcome Measure
Number of Participants With Disabling Stroke
Outcome Description
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.
0 No stroke symptoms 1-4 Minor stroke 5-15 Moderate stroke 16-20 Moderate to severe stroke 21-42 Severe stroke.
Outcome Time Frame
From randomization up to 97 days
Outcome Measure
Change in NIHSS
Outcome Description
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.
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.
Outcome Time Frame
Visit 1 (Enrolment)
Outcome Measure
EQ-5D at Visit 1 (Enrolment)
Outcome Description
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.
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.
Outcome Time Frame
Visit 2 (Day 7+-2d)
Outcome Measure
EQ-5D at Visit 2 (Day 7+-2d)
Outcome Description
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.
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.
Outcome Time Frame
End of treatment visit (Day 90+-7d)
Outcome Measure
EQ-5D (EuroQol Five Dimensions Questionnaire) at End of Treatment Visit
Outcome Description
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.
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.
Outcome Time Frame
Premature treatment discontinuation visit(<15 days after last dose)
Outcome Measure
EQ-5D (EuroQol Five Dimensions Questionnaire) at Premature Treatment Discontinuation Visit
Outcome Description
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.
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.
Outcome Time Frame
From randomization up to 97 days
Outcome Measure
Number of Participants With PLATO Major Bleeding Event
Outcome Description
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).
Outcome Time Frame
Time from first dose and up to and including 7 days following the date of last dose of the study
Outcome Measure
Number of Participants With Premature Discontinuation of Study Drug Due to Any Bleeding Adverse Event
See Also Links
Url
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
130
Minimum Age Number (converted to Years and rounded down)
40
Investigators
Investigator Type
Principal Investigator
Investigator Name
Mellanie Springer
Investigator Email
mspringe@montefiore.org
Investigator Phone
718-420-6444