Patients presenting with acute ischaemic stroke; 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 NIHSS score of ? 4 - 26 with clinical signs of hemispheric infarction; 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.
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 or CT with contrast agents; infarct core >1/3 MCA territory qualitatively or >100mls quantitatively (determined by DWI lesion on MR); 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; 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; 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 a 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 agent oral platelet inhibitors (clopidogrel 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 which poses risk in the opinion of the investigator; exposure to a thrombolytic agent within the previous 72 hours.