EARLY 3-months Aggrenox Treatment Started Within 24 Hrs of Ischemic Stroke Onset vs. After One Week 100 mg ASA

Study Overview
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Brief Summary
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German stroke units are hesitating to use Aggrenox for secondary ischaemic stroke / transient ischaemic attack (TIA) prevention in a sub-acute treatment setting. They argue that clinical experience with sub-acute Aggrenox treatment is limited and poorly documented when compared with sub-acute acetylsalicylic acid (ASA) treatment. However, long term treatment (started after 3-6 months after stroke/TIA) with Aggrenox was safe and superior to ASA treatment in preventing recurrent strokes. There is no evidence for ASA to prevent from neurological progression after stroke during the first 3 months. Results from a cohort study suggest that starting Aggrenox within 72 hours after stroke predicts clinical improvement in the National Institute of Health Stroke Scale (NIHSS) at discharge from the hospital. Dipyridamole suppresses acute inflammatory responses to stroke. This study is designed to investigate the tolerability and efficacy of a secondary stroke prevention treatment with Aggrenox when initiated within 24 hours of stroke onset on a stroke unit compared to later initiation after a 7 day ASA treatment and outside off a stroke unit setting.

Official Title
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EARLY: Prospective, Randomised, National, Multi-centre, Open-label, Blinded Endpoint Study to Compare Aggrenox b.i.d. (200 mg Dipyridamole MR + 25 mg Acetylsalicylic Acid) When Started Within 24 Hours of Stroke Onset on an Acute Stroke Unit, and Aggrenox b.i.d. When Started After a 7-day Therapy With ASA 100 mg Once Daily Outside Off an Acute Stroke Unit, in Symptomatic Ischaemic Stroke Patients Over a Three Months Treatment Period an Exploratory Study

Conditions
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Cerebrovascular Accident

Intervention / Treatment
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* Drug: Aggrenox bid (ASA 25mg/Dipyridamole ER 200mg)
* Drug: ASA 100 mg qd


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -Clinical diagnosis of ischaemic stroke causing a measurable neurological deficit defined as impairment of language, motor function, cognition and/or gaze, vision or neglect. Symptoms must be distinguishable from an episode of generalised ischaemia (i.e. syncope), seizure, or migraine disorder. Main inclusion criteria: Patients at risk of stroke who have had transient ischaemia of the brain or completed ischaemic stroke due to thrombosis Symptoms of ischaemic attack began less than 24 hours prior to study medication start, are to be present for at least 30 minutes and have not significantly improved before start of treatment Patients are eligible for platelet inhibiting treatment National Institute of Health Stroke Scale (NIHSS) between 5 and 20 (at pre-screening and screening) Actual Modified Rankin Scale (mRS) (at baseline) is worse than retrospective mRS (before stroke) A contraindication for stroke lysis is given Patients are able to give (at least oral) informed consent and to swallow either medication Exclusion Criteria: Hypersensitivity to any of the components of the product or salicylates. Patients with active gastric or duodenal ulcers or with bleeding disorders. Pregnancy during the third trimester. Lysis therapy. A platelet inhibiting therapy with Acetylsalicylic Acid (ASA) doses of more than 100 mg per day, or with clopidogrel of any dose has been planned or started. Time of onset of stroke symptoms is unknown (when a stroke happened during night-/sleeping time, bedtime is assumed as time of onset)

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Intervention Model: Parallel Assignment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Aggrenox bid (ASA 25mg/Dipyridamole ER 200mg)|nan|
|Drug: ASA 100 mg qd|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Telephone Modified Rankin Scale (Centralised, Blinded Assessment) | The modified Rankin Scale (mRS) is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke. The scale runs from 0-6, running from perfect health without symptoms to death. Best value - 0 (No symptoms), worst value - 6 (Dead) | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in NIHSS (National Institutes of Health Stroke Scale) | The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42 (dead) | Baseline and 90 days | 
| Patients With Relevant Event (Death, Non-fatal Stroke, Transient Ischaemic Attack (TIA), Myocardial Infarction (MI), Bleeding) |  | 90 days | 
| Telephone Modified Rankin Scale (Centralised, Blinded Assessment) at Day 8 | The modified Rankin Scale (mRS) is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke. The scale runs from 0-6, running from perfect health without symptoms to death. Best value - 0 (No symptoms), worst value - 6 (Dead) | 8 days | 
| Change From Baseline in NIHSS (National Institutes of Health Stroke Scale) at Day 8 | The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42 (dead) | Baseline and 8 days | 
| Change of Special Biochemical Laboratory Value- CRP | Changes of special biochemical laboratory values (CRP) from baseline to day 8 - centralised, blinded assessment by a specialised central clinical laboratory | 8 days | 
| Change of Special Biochemical Laboratory Value- MMP-9 | Changes of special biochemical laboratory value (MMP-9) from baseline to day 8 - centralised, blinded assessment by a specialised central clinical laboratory | 8 days | 
| Change of Special Biochemical Laboratory Value - MCP-1 | Changes of special biochemical laboratory value (MCP-1) from baseline to day 8 - centralised, blinded assessment by a specialised central clinical laboratory | 8 days | 
| Change From Baseline in FLAIR (Fluid-Attenuated Inversion Recovery) at Day 8 | MRI was performed to assess growth in stroke lesion volume by fluid-attenuated inversion recovery (FLAIR). | Baseline and day 8 | 
| Change From Baseline in FLAIR (Fluid-Attenuated Inversion Recovery) at Day 90. | MRI was performed to assess growth in stroke lesion volume by fluid-attenuated inversion recovery (FLAIR). | Baseline and day 90 | 
| Change From Baseline in DWI (Diffuse-Weighted Imaging) at Day 8 | MRI was performed to assess growth in stroke lesion volume by diffusion-weighted imaging (DWI). DWI was to give evidence of the development of the ischaemic lesion corresponding to the evolved stroke. | Baseline and day 8 | 
| Change From Baseline in DWI (Diffuse-Weighted Imaging) at Day 90 | MRI was performed to assess growth in stroke lesion volume by diffusion-weighted imaging (DWI). DWI was to give evidence of the development of the ischaemic lesion corresponding to the evolved stroke. | Baseline and day 90 |