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


Phase 2 Results N/A

Eligibility Criteria

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