Ischaemic stroke MedDRA version: 17.1 Level: LLT Classification code 10055221 Term: Ischemic stroke System Organ Class: 10029205 - Nervous system disorders MedDRA version: 17.1 Level: PT Classification code 10061256 Term: Ischaemic stroke System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Actilyse
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: ALTEPLASE
CAS Number: 105857-23-6
Concentration unit: mg milligram(s)
Concentration type: eq
Sponsors
The Florey Institute of Neuroscience and Mental Health
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients presenting with hemispheric 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 (or as per local requirements) 4. Treatment onset can commence after 4.5 hours and up to and including 9 hours after stroke onset according to registered product information, or greater than 3 hours up to and including 9 hours according to locally accepted guidelines 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. 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. 6. Significant neurological deficit (eg NIHSS score of = 4 – 26) with clinical signs of hemispheric infarction. 7. Penumbral mismatch – A “hypoperfusion to core” lesion 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 CTCBF core lesion. 8. An ischaemic core lesion volume of less than or equal to 70 ml using MRDWI or CT-CBF Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 300
Exclusion 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 1/3 MCA territory qualitatively 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 > 1.7) 13. Use of heparin, except for low dose subcutaneous heparin, in the previous 48 hours and a prolonged activated 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 or dual agent oral platelet inhibitors (clopidogrel and/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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To test the hypothesis that ischaemic stroke patients of similar age and stroke severity selected with significant penumbral mismatch at 4.5 - 9 hours post onset of stroke or after ‘wake up stroke’ (WUS) will have improved clinical outcomes when given intravenous tPA compared to placebo.;Secondary Objective: Not applicable;Primary end point(s): Modified Rankin Scale (mRS) 0 – 1 at 90 days;Timepoint(s) of evaluation of this end point: 90 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Categorical shift in mRS at 90 days Change in = 8 NIHSS points or reaching = 1 on this scale Death due to any cause Symptomatic ICH Reperfusion at 24 hrs post stroke Recanalisation at 24 hrs post stroke Infarct growth within 24 hrs Recurrent stroke at 3 months;Timepoint(s) of evaluation of this end point: 0 to 90 days | — |
Countries
Australia, Finland, New Zealand, Taiwan
Contacts
Public ContactRachael McCoy
The Florey Institute of Neuroscience and Mental Health
Outcome results
None listed