Participants presenting with acute ischaemic stroke
Participant, family member or legally responsible person depending on local ethics requirements has given informed consent
Participant's age is ≥ 18 years
Treatment onset can commence within ≥ 3 to 9 hours after stroke onset according to registered product information, or within 4.5 to 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 awake 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 midpoint 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 midpoint as described
NIHSS score of ≥ 4 to 26 with clinical signs of hemispheric infarction
Penumbral imaging ‐ using a Tmax > 6‐second delay, a perfusion (PWI) lesion volume to diffusion (DWI) lesion volume ratio > 1.2, a DWI volume ≤ 70 mL, and a perfusion lesion volume‐diffusion lesion volume difference > 10 mL
Patients may be consented before or after penumbral screening depending upon local practice. The entire cohort of patients consented into the study will be followed up with clinical assessments and biomarker studies regardless of eligibility for randomisation to treatment based on penumbral mismatch criteria
Intracranial haemorrhage identified by CT or MRI
Rapidly improving symptoms, particularly if in the judgement of the managing clinician improvement is likely to result in the patient having an NIHSS score of < 4 at randomisation
Pre‐stroke mRS score of ≥ 2 (indicating previous disability)
Contraindication to imaging with magnetic resonance with contrast agents
Infarct core > 1/3 middle cerebral artery territory qualitatively
Participation in any investigational study in the previous 30 days
Any terminal illness such that the 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 uraemic syndrome or thrombotic thrombocytopenic purpura). The judgement is left to the discretion of the investigator
Pregnant women (clinically evident)
Previous stroke within last 3 months
Recent past history or clinical presentation of intracerebral haemorrhage, subarachnoid haemorrhage, arteriovenous malformation, aneurysm, or cerebral neoplasm. At the discretion of each investigator
Current use of oral anticoagulants and a prolonged prothrombin time (INR > 1.6)
Use of heparin, except for low‐dose subcutaneous heparin, in the previous 48 hours and an activated prolonged partial thromboplastin time exceeding the upper limit of the local laboratory normal range
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
Clinically significant hypoglycaemia
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
Hereditary or acquired haemorrhagic diathesis
Gastrointestinal or urinary bleeding within the preceding 21 days
Major surgery within the preceding 14 days that poses risk in the opinion of the investigator
Exposure to a thrombolytic agent within the previous 72 hours
