Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis- (ATTEST)

Inclusion Criteria: * clinical diagnosis of supratentorial acute ischaemic stroke with score of at least 1 on the NIH Stroke Scale * male or non pregnant female \>=18 years * within 4.5 hours of onset as defined by time since last known well * CT perfusion and CT Angiogram examination acquired prior to treatment Exclusion Criteria: * Contraindications to thrombolytic drug treatment for stroke * Evidence of intracranial haemorrhage or significant non-stroke intracranial pathology (including central nervous system neoplasm, aneurysm or arteriovenous malformation) on pre-treatment CT * Established hypodensity on pre-treatment brain CT of more than one third of the middle cerebral artery territory or Alberta Stroke Programme Early CT (ASPECT) Score \<4 (sulcal effacement or loss of grey-white differentiation in cortical territories alone are not counted towards ASPECT score) * Hypodensity consistent with recent cerebral ischaemia other than the presenting event * Very severe stroke (eg NIHSS\>25) * systolic blood pressure (BP)\> 185 or diastolic BP\> 110 mm Hg, or aggressive management (intravenous pharmacotherapy) necessary to reduce BP to these limits * If on warfarin, International Normalised Ratio (INR) \<1.4 * Current prescription of non-warfarin oral anticoagulant drugs * Significant abnormality of coagulation parameters pre-treatment (prolonged INR or activated partial thromboplastin time (APTT), or platelet count \<100,000/mm3) * administration of heparin within the previous 48 hours and a thromboplastin time exceeding the upper limit of normal for laboratory, or use of therapeutic dose low molecular weight heparin within 48h * Clinical history suggestive of subarachnoid haemorrhage even if no blood is evident on CT * Risk of bleeding (Major surgery within previous 1 month; intracranial or spinal surgery; recent trauma to the head or cranium; prolonged cardiopulmonary resuscitation (\> 2 minutes) within the past 2 weeks; acute pericarditis and/or subacute bacterial endocarditis; acute pancreatitis; severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis; active peptic ulceration; any known history of haemorrhagic stroke or stroke of unknown origin; arterial aneurysm and known arteriovenous malformation) * Dependent (mRS 3-5) pre-stroke * Blood glucose \<2 mmol/l or \>18 mmol/l * Seizure at onset of symptoms unless brain imaging identifies positive evidence of significant brain ischaemia (eg CTA confirmed arterial occlusion, early ischaemic change on plain CT, hypoperfusion on CTP) * Pregnancy * Known impaired renal function (estimated Glomerular Filtration Rate \<30 ml/min) precluding contrast CT * Known allergy to radiological contrast * History of allergies to active substances in either trial medication, or to excipients including gentamicin * Severe concurrent medical condition that would prevent participation in study procedures (e.g. cardia failure with severe pulmonary oedema)or with life expectancy \<=3 months