The principle research question is: in patients with acute ischaemic stroke eligible for intravenous (IV) thrombolysis, is tenecteplase superior in efficacy to alteplase, based on functional outcome as assessed by modified Rankin Scale distribution at day 90?

Inclusion criteria:

• Eligible for intravenous thrombolysis.
• Male or non-pregnant female ≥18 years of age.
• <4.5h after symptom onset.
• Consent of patient or legal representative.
• Independent prior to the stroke (estimated modified Rankin Scale 0-2).

Exclusion criteria:

• Eligible for intravenous thrombolysis: Evidence of intracranial haemorrhage or significant non-stroke intracranial pathology likely to account for clinical presentation or represent a risk of intracerebral haemorrhage (eg Central Nervous System neoplasm) on pre-treatment computerised tomography (CT) scan; Stroke within the previous 14 days, thrombolytic therapy within the past 14 days, or hypodensity on pre-treatment computerised tomography (CT) scan consistent with recent cerebral ischaemia other than the presenting event; Systolic blood pressure more than 185 or diastolic blood pressure more than 110 mmHg, or aggressive management (intravenous pharmacotherapy) necessary to reduce blood pressure to these limits; Clinical history suggestive of subarachnoid haemorrhage even if no blood is evident on computerised tomography (CT) scan; High risk of haemorrhage, including major surgery, trauma or gastrointestinal or urinary tract haemorrhage within the previous 21 days; Arterial puncture at a non-compressible site within the previous 7 days; Prolonged cardiopulmonary resuscitation (> 2 minutes) within the previous 14 days; 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; Known history of haemorrhagic stroke; Known defect of clotting or platelet function (other than antiplatelet therapy); Hypo- or hyperglycaemia (blood glucose <2 mmol/l or >18 mmol/l) sufficient to account for neurological symptoms; Seizure at onset of symptoms unless brain imaging identifies positive evidence of significant brain ischaemia (eg early ischaemic change or hyperdense vessel on plain computerised tomography (CT) scan, computerised tomography angiography (CTA) scan confirmed arterial occlusion); Pregnancy (for women of child-bearing potential a negative pregnancy test will be required prior to randomisation); Inadequate haemostasis: Taking warfarin and international normalised ratio (INR) >1.3, Taking a Direct Oral Anticoagulant (dabigatran, rivaroxaban, apixaban, edoxaban) unless known to be >12 hours since last dose and with normal coagulation assays, Low molecular weight heparin (at doses other than prophylaxis of venous thromboembolism) administered within the preceding 48 hours, Unfractionated heparin administered within the previous 48 hours and activated partial thromboplastin time (APTT) is prolonged.
• Any major medical condition likely to limit survival to day 90.
• Unavailable for day 90 follow-up.