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

Cerebrovascular Accident Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00562588
• Other study ID #: 9.182
• Status: Completed
• Phase: Phase 4
• First received: July 6, 2007
• Last updated: January 31, 2014
• Start date: July 2007

Study information

• Verified date: January 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: BfArM (Bundesagentur fuer Arzneimittel und Medizinalprodukte)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 551
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cerebrovascular Accident
• Stroke

Intervention

Drug:
• Aggrenox bid (ASA 25mg/Dipyridamole ER 200mg)

• ASA 100 mg qd

Locations

Country	Name	City	State
Germany	9.182.1 Boehringer Ingelheim Investigational Site	Bad Homburg

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	Patients With Relevant Event (Death, Non-fatal Stroke, Transient Ischaemic Attack (TIA), Myocardial Infarction (MI), Bleeding)		90 days	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

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