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

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00562588
First received: July 6, 2007
Last updated: January 31, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Cerebrovascular Accident
Drug: Aggrenox bid (ASA 25mg/Dipyridamole ER 200mg)
Drug: ASA 100 mg qd
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Telephone Modified Rankin Scale (Centralised, Blinded Assessment) [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • Change From Baseline in NIHSS (National Institutes of Health Stroke Scale) [ Time Frame: Baseline and 90 days ] [ Designated as safety issue: No ]
    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)

  • Patients With Relevant Event (Death, Non-fatal Stroke, Transient Ischaemic Attack (TIA), Myocardial Infarction (MI), Bleeding) [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • Telephone Modified Rankin Scale (Centralised, Blinded Assessment) at Day 8 [ Time Frame: 8 days ] [ Designated as safety issue: No ]
    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)

  • Change From Baseline in NIHSS (National Institutes of Health Stroke Scale) at Day 8 [ Time Frame: Baseline and 8 days ] [ Designated as safety issue: No ]
    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)

  • Change of Special Biochemical Laboratory Value- CRP [ Time Frame: 8 days ] [ Designated as safety issue: No ]
    Changes of special biochemical laboratory values (CRP) from baseline to day 8 - centralised, blinded assessment by a specialised central clinical laboratory

  • Change of Special Biochemical Laboratory Value- MMP-9 [ Time Frame: 8 days ] [ Designated as safety issue: No ]
    Changes of special biochemical laboratory value (MMP-9) from baseline to day 8 - centralised, blinded assessment by a specialised central clinical laboratory

  • Change of Special Biochemical Laboratory Value - MCP-1 [ Time Frame: 8 days ] [ Designated as safety issue: No ]
    Changes of special biochemical laboratory value (MCP-1) from baseline to day 8 - centralised, blinded assessment by a specialised central clinical laboratory

  • Change From Baseline in FLAIR (Fluid-Attenuated Inversion Recovery) at Day 8 [ Time Frame: Baseline and day 8 ] [ Designated as safety issue: No ]
    MRI was performed to assess growth in stroke lesion volume by fluid-attenuated inversion recovery (FLAIR).

  • Change From Baseline in FLAIR (Fluid-Attenuated Inversion Recovery) at Day 90. [ Time Frame: Baseline and day 90 ] [ Designated as safety issue: No ]
    MRI was performed to assess growth in stroke lesion volume by fluid-attenuated inversion recovery (FLAIR).

  • Change From Baseline in DWI (Diffuse-Weighted Imaging) at Day 8 [ Time Frame: Baseline and day 8 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in DWI (Diffuse-Weighted Imaging) at Day 90 [ Time Frame: Baseline and day 90 ] [ Designated as safety issue: No ]
    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.


Enrollment: 551
Study Start Date: July 2007
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00562588

Locations
Germany
9.182.1 Boehringer Ingelheim Investigational Site
Bad Homburg, Germany
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00562588     History of Changes
Other Study ID Numbers: 9.182
Study First Received: July 6, 2007
Results First Received: January 29, 2010
Last Updated: January 31, 2014
Health Authority: Germany: BfArM (Bundesagentur fuer Arzneimittel und Medizinalprodukte)

Additional relevant MeSH terms:
Cerebral Infarction
Stroke
Brain Infarction
Brain Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Dipyridamole
Aspirin, dipyridamole drug combination
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Vasodilator Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on April 14, 2014