Acute Ischaemic Stroke MedDRA version: 20.0 Level: PT Classification code 10061256 Term: Ischaemic stroke System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Actilyse (Alteplase)
Product Name: Actilyse
Pharmaceutical Form: Powder and solvent for solution for injection/infusion
INN or Proposed INN: Alteplase
Other descriptive name: recombinant t
Sponsors
University of Newcastle
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General Inclusion Criteria: 1. Patients presenting with acute hemispheric ischaemic stroke eligible using standard criteria to receive IV tPA within 4.5 hours of stroke onset. 2. Patient, family member or legally responsible person depending on local ethics requirements has given informed consent. 3. Patient’s age is = 18 years. Imaging inclusion criteria: 1. Vessel occlusion on CT or MR angiography is NOT a requirement for inclusion into the study. However, the presence or absence of ICA occlusion on CT or MR angiography will be required to be noted for randomisation stratification. 2. Presence of penumbra - Using CTP or perfusion MR, mismatch between the perfusion lesion measured on Tmax > 6 seconds (or Delay Time > 3 seconds) and the infarct core lesion measured on CTP relative cerebral blood flow (relCBF) or diffusion MR a) Mismatch ratio between Tmax (or Delay Time) perfusion lesion and infarct core lesion of > 1.8 b) Penumbra volume > 15 mL (Tmax or Delay Time lesion volume – infarct core lesion volume) 3. Infarct core lesion volume 10 seconds or Delay Time > 8 seconds. Large volumes of severely hypoperfused tissue are indicative of a poor response to treatment. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 800 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 224
Exclusion criteria
Exclusion criteria: 1. Intracranial haemorrhage (ICH) identified on baseline CT or MRI. 2. Rapidly improving symptoms at the discretion of the investigator. 3. Pre-stroke mRS score of = 2 (indicating previous disability). 4. Participation in any investigational study in the previous 30 days. 5. Any terminal illness such that patient would not be expected to survive more than one year. 6. Any condition that, in the judgement of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study. 7. Pregnant women. 8. Previous stroke within last three months. 9. 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. 10. Current use of vitamin K based oral anticoagulants (e.g. warfarin) and a prolonged prothrombin time (INR > 1.5). 11. Current use of novel oral anticoagulants (NOACs) (i.e. dabigatran, rivaroxaban, or apixiban). 12. 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. 13. 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. 14. Clinically significant hypoglycaemia. 15. Uncontrolled hypertension defined by a blood pressure > 185 mmHg systolic or > 110 mmHg diastolic on at least two 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. 16. Hereditary or acquired haemorrhagic diathesis. 17. Gastrointestinal or urinary bleeding within the preceding 21 days. 18. Major surgery within the preceding 14 days which poses risk in the opinion of the investigator. 19. Exposure to a thrombolytic agent within the previous 72 hours 20. An extracranial or intracranial internal carotid artery occlusion or a proximal M1 middle cerebral artery occlusion which, in the judgment of the investigator, would be more appropriately treated with combined intravenous intra-arterial therapy, where the intra-arterial therapy can be accessed and delivered within a rapid time frame.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to test the hypothesis that patients with acute hemispheric ischaemic stroke who have significant penumbra (area of potentially salvageable tissue surrounding the stroke) and a relatively small infarct core on perfusion CT or MRI within 4.5 hours of symptom onset will have less disability at 3 months when treated with IV Tenecteplase 0.25 mg/kg compared to IV Alteplase 0.9mg/kg. ;Secondary Objective: The secondary endpoints include: -Efficacy of Tenecteplase: Specifically restoration of blood flow (reperfusion) at 24 hours measured by CT perfusion scan, early clinical improvement (NIHSS score reduction at 24 hours), modified Rankin Scale (mRS) of 0-1 and 0-2 at 3 months, categorical shift in mRS at 3 months, and blood flow restoration and infarct growth at 24 hours. -Safety: Symptomatic intracerebral haemorrhage (bleeding in the brain) occurrance, death due to any cause, mRS of 5-6 at 3 months;Primary end point(s): The primary outcome is Modified Rankin Scale (mRS) 0-1 at 3 months (no disability).;Timepoint(s) of evaluation of this end point: 3 months post stroke | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy Endpoints: -Reperfusion at 24 hours post stroke* -Early clinical improvement (reduction in acute – 24 hour NIHSS score)* -Modified Rankin Scale (mRS) 0-1 at 3 months (adjusted for baseline age and NIHSS) -Modified Rankin Scale 0-2 at 3 months -Categorical shift in mRS at 3 months -Infarct growth at 24 hours -Recanalisation at 24 hours post stroke. *Note that there will be a planned interim efficacy analysis after 200 patients for the following endpoints: reperfusion at 24 hours post stroke, NIHSS improvement at 24 hours and mRS 0-1 at 3 months post stroke. Safety Endpoints: -Symptomatic intra-cerebral haemorrhage (sICH)* -Death due to any cause -Modified Rankin Scale (mRS) 5-6 at 3 months (severe disability or death). *Symptomatic intracerebral haemorrhage (sICH) is defined as “Intracerebral haemorrhage (parenchymal haematoma type 2 - PH2 within 36 hours of treatment) combined with neurological deterioration leading to an increase of =4 points on the NIHSS from baseline, or the lowest NIHSS value between baseline and 24 hours”.;Timepoint(s) of evaluation of this end point: Reperfusion, Early Clinical Improvement (reduction in acute-24hour NIHSS score), Infarct Growth and Recanalisation are at 24-hours post-stroke mRS 0-1, 0-2, 5-6 and a catagorical shift in mRS are at 3 months post-stroke | — |
Countries
Australia, Belgium, Canada, Germany, New Zealand, Spain, Sweden, Taiwan, United Kingdom
Contacts
Public ContactChristopher Levi
University of Newcastle
Outcome results
None listed