Extending the Time for Thrombolysis in Emergency Neurological Deficits
Information source: National Stroke Research Institute, Australia
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Stroke
Intervention: Tissue Plasminogen Activator (Drug); Placebo (Drug)
Phase: Phase 3
Status: Not yet recruiting
Sponsored by: National Stroke Research Institute, Australia Official(s) and/or principal investigator(s):
Geoffrey Donnan, MD FRACP, Principal Investigator, Affiliation: National Stroke Research Institute, Australia
Stephen Davis, MD FRACP, Principal Investigator, Affiliation: University of Melbourne
Overall contact:
Sue Bates, BSc(Hons), Phone: +61 3 9496 2754, Email: sbates@neurotrialsaustralia.com
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.
Clinical Details
Official title: Extending the Time for Thrombolysis in Emergency Neurological Deficits
Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: Modified Rankin Scale
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Patients presenting with acute ischaemic stroke
2. Patient, family member or legally responsible person depending on local ethics
requirements has given informed consent
3. Patient's age is ≥18 years
4. 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)
5. 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.
NIHSS score of ≥ 4 - 26 with clinical signs of hemispheric infarction.
6. Penumbral imaging** - Using a Tmax ≥ 6 second delay, a perfusion volume to infarct
core ratio (PWI) of 1. 2, and a perfusion lesion minimum volume of 20 ml.
- 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:
1. Intracranial haemorrhage (ICH) identified by CT or MRI
2. 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
3. Pre-stroke MRS score of ≥ 2 (indicating previous disability)
4. Contra indication to imaging with MR or CT with contrast agents
5. Infarct core >1/3 MCA territory qualitatively or >100mls quantitatively (determined
by DWI lesion on MR).
6. Participation in any investigational study in the previous 30 days
7. Any terminal illness such that patient would not be expected to survive more than 1
year
8. 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.
9. Pregnant women (clinically evident)
10. Previous stroke within last three months
11. Recent past history or clinical presentation of ICH, subarachnoid haemorrhage (SAH),
arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm. At the discretion
of each Investigator.
12. Current use of oral anticoagulants and a prolonged prothrombin time (INR > 1. 6)
13. Use of heparin, except for low dose subcutaneous heparin, in the previous 48 hours
and a prolonged partial thromboplastin time exceeding the upper limit of the local
laboratory normal range.
14. Use of glycoprotein IIb - IIIa inhibitors within the past 72 hours. Use of single
agent oral platelet inhibitors (clopidogrel or low-dose aspirin) prior to study entry
is permitted.
15. Clinically significant hypoglycaemia.
16. Uncontrolled hypertension defined by a blood pressure > 185 mmHg systolic or >110
mmHg diastolic on at least 2 separate occasions at least 10 minutes apart, or
requiring aggressive treatment to reduce the blood pressure to within these limits.
The definition of "aggressive treatment" is left to the discretion of the responsible
Investigator.
17. Hereditary or acquired haemorrhagic diathesis
18. Gastrointestinal or urinary bleeding within the preceding 21 days
19. Major surgery within the preceding 14 days which poses risk in the opinion of the
investigator.
20. Exposure to a thrombolytic agent within the previous 72 hours
Locations and Contacts
Sue Bates, BSc(Hons), Phone: +61 3 9496 2754, Email: sbates@neurotrialsaustralia.com
Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia
Additional Information
National Stroke Research Institute
Last updated: April 22, 2009
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