Clinical trial NCT00562588: EARLY 3-months Aggrenox Treatment Started Within 24 Hrs of Ischemic Stroke Onset vs. After One Week 100 mg ASA
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cerebrovascular Accident
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2007-11-22
Enrollment: 551
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Telephone Modified Rankin Scale (Centralised, Blinded Assessment)
timeFrame: 90 days
Secondary outcomes:
measure: Change From Baseline in NIHSS (National Institutes of Health Stroke Scale)
timeFrame: Baseline and 90 days
measure: Patients With Relevant Event (Death, Non-fatal Stroke, Transient Ischaemic Attack (TIA), Myocardial Infarction (MI), Bleeding)
timeFrame: 90 days
measure: Telephone Modified Rankin Scale (Centralised, Blinded Assessment) at Day 8
timeFrame: 8 days
measure: Change From Baseline in NIHSS (National Institutes of Health Stroke Scale) at Day 8
timeFrame: Baseline and 8 days
measure: Change of Special Biochemical Laboratory Value- CRP
timeFrame: 8 days
measure: Change of Special Biochemical Laboratory Value- MMP-9
timeFrame: 8 days
measure: Change of Special Biochemical Laboratory Value - MCP-1
timeFrame: 8 days
measure: Change From Baseline in FLAIR (Fluid-Attenuated Inversion Recovery) at Day 8
timeFrame: Baseline and day 8
measure: Change From Baseline in FLAIR (Fluid-Attenuated Inversion Recovery) at Day 90.
timeFrame: Baseline and day 90
measure: Change From Baseline in DWI (Diffuse-Weighted Imaging) at Day 8
timeFrame: Baseline and day 8
measure: Change From Baseline in DWI (Diffuse-Weighted Imaging) at Day 90
timeFrame: Baseline and day 90
Other outcomes:
Locations:
city: Bad Homburg
country: Germany
facility: 9.182.1 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Dengler R, Diener HC, Schwartz A, Grond M, Schumacher H, Machnig T, Eschenfelder CC, Leonard J, Weissenborn K, Kastrup A, Haberl R; EARLY Investigators. Early treatment with aspirin plus extended-release dipyridamole for transient ischaemic attack or ischaemic stroke within 24 h of symptom onset (EARLY trial): a randomised, open-label, blinded-endpoint trial. Lancet Neurol. 2010 Feb;9(2):159-66. doi: 10.1016/S1474-4422(09)70361-8. Epub 2010 Jan 7.