Extending the Time for Thrombolysis in Emergency Neurological Deficits

Neuroscience Trials Australia1 site in 1 country45 target enrollmentDecember 6, 2012

ConditionsStroke

InterventionsTissue Plasminogen Activator (Alteplase)Placebo

DrugsTissue Plasminogen Activator (Alteplase)Placebo

Overview

Phase: Phase 3
Intervention: Tissue Plasminogen Activator (Alteplase)
Conditions: Stroke
Sponsor: Neuroscience Trials Australia
Enrollment: 45
Locations: 1
Primary Endpoint: Modified Rankin Scale (mRS) 0-1
Status: Completed
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The primary hypothesis being tested in this trial is that ischaemic stroke patients selected with significant penumbral mismatch (according to imaging criteria) at 4.5 (or 3 hours depending on local guidelines) - 9 hours post onset of stroke or after 'wake up stroke' (WUS) will have improved clinical outcomes when given intravenous tissue plasminogen activator (tPA) compared to placebo.

Registry

clinicaltrials.gov

Start Date

December 6, 2012

End Date

August 22, 2018

Last Updated

7 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Neuroscience Trials Australia

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients presenting with hemispheric acute ischaemic stroke
•Patient, family member or legally responsible person depending on local ethics requirements has given informed consent
•Patient's age is ≥18 years (or as per local requirements)
•Treatment onset can commence within 4.5 - 9 hours after stroke onset according to registered product information, or within 3 - 9 hours according to locally accepted guidelines.
•Patients who wake with stroke may be included if neurological and other exclusion criteria are satisfied. These 'wake up' strokes are defined as having no symptoms at sleep onset, but stroke symptoms on waking. The time of stroke onset is to be taken as the mid-point between sleep onset (or last known to be normal) and time of waking. The maximum time window for randomisation is then 9 hours from the mid-point as described.
•Significant neurological deficit (eg. NIHSS score of ≥ 4 - 26) with clinical signs of hemispheric infarction.
•Penumbral mismatch - A "hypo-perfusion to core" volume ratio of greater than 1.2, and an absolute difference greater than 10ml (using a Magnetic Resonance (MR) or Computed Tomography (CT) Tmax \> 6 second delay), between perfusion lesion and MR-DWI or Computed Tomography-Cerebral Blood Flow (CT-CBF) core lesion.
•An infarct core lesion of less than or equal to 70ml using MR-DWI or CT-CBF

Exclusion Criteria

•Intracranial haemorrhage (ICH) identified by CT or MRI
•Rapidly improving symptoms, particularly if in the judgment of the managing clinician that the improvement is likely to result in the patient having an NIHSS score of \< 4 at randomization
•Pre-stroke MRS score of ≥ 2 (indicating previous disability)
•Contra indication to imaging with contrast agents
•Infarct core \>1/3 Middle Cerebral Artery (MCA) territory qualitatively
•Participation in any investigational study in the previous 30 days
•Any terminal illness such that patient would not be expected to survive more than 1 year
•Any condition that could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study (this applies to patients with severe microangiopathy such as haemolytic uremic syndrome or thrombotic thrombocytopenic purpura). The judgment is left to the discretion of the Investigator.
•Pregnant women (clinically evident)
•Previous stroke within last three months

Arms & Interventions

intravenous tissue plasminogen activator

Intervention: Tissue Plasminogen Activator (Alteplase)

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

Modified Rankin Scale (mRS) 0-1

Time Frame: 3 months

Secondary Outcomes

Categorical shift in modified Rankin Score (mRS)(3 months)
Change in ≥ 8 National Institutes of Health Stroke Scale (NIHSS) points or reaching ≤ 1 on this scale(3 months)
Death due to any cause(3 months)
Symptomatic Intracerebral Hemorrhage (ICH)(24 hours)
Reperfusion(24 hours)
Recanalisation(24 hours)
Infarct growth(24 hours)
Recurrent stroke(3 and 12 months)