Extending the Time for Thrombolysis in Emergency Neurological Deficits

Neuroscience Trials Australia22 sites in 3 countries180 target enrollmentJune 2010

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: 180
Locations: 22
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 (measured by MRI criteria) at 3 - 9 hours post onset of stroke will have improved clinical outcomes when given intravenous tissue plasminogen activator (tPA) compared to placebo.

Registry

clinicaltrials.gov

Start Date

June 2010

End Date

August 27, 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
•Treatment onset can commence within ≥ 3 - 9 hours after stroke onset according to registered product information, or within 4.5 - 9 hours according to locally accepted guidelines\*.
•(\*Guidelines are currently under international review - advisory statement issued by the Stroke Council, American Heart Association and American Stroke Association)
•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.
•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 MR or CT Tmax \> 6 second delay) between perfusion lesion and MR-DWI or CT-CBF core lesion.
•An ischaemic core lesion volume of less than or equal to 70 ml using MR-DWI or CT-CBF \*\* Patients may be consented before or after penumbral screening depending upon local practice. The entire cohort of patients consented onto the study will be followed up with clinical assessments and biomarker studies regardless of eligibility for randomisation to treatment based on penumbral mismatch criteria

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 MR with contrast agents
•Infarct core \>1/3 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