intra-arterial versus systemic thrombolysis for acute ischemic stroke

Conditions: Stroke; Cerebrovascular Accident

Summary: synthesis is a pragmatic multicenter randomized controlled trial (rct), open-label, with blinded follow-up aiming to determine whether loco-regional intra-arterial (ia) with recombinant tissue-plasminogen activator (rt-pa) and/or mechanical devices, as compared with systemic intravenous (i.v.) infusion of rt-pa within 3 hours of ischemic stroke, increases the proportion of independent survivors at 3 months.

eligibility criteria:patients with symptomatic, ct verified, acute ischemic stroke, being able to initiate iv rt-pa within 3 hours and ia thrombolysis within 6 hours of stroke onset, when uncertainty about appropriateness the two approaches exists as established by the treating physician. eligible patients are randomized to receive either 0.9 mg/kg (max 90 mg) iv rt-pa (control arm) or up to 0.9 mg/kg ia rt-pa (max 90 mg) over 60 minutes into the thrombus, eventually associated with clot mechanical disaggregation/dislocation or retraction/aspiration. mechanical thrombolysis is possible also without the use of rt-pa. the procedural choices of the interventional neuroradiologist depend on the type of occlusion, circumstances and experience. the study is designed to detect or disprove (alpha=5% and power probability=80%) a 15% absolute difference between the treatment groups in the percentage of patients with a favourable outcome (modified rankin scale score = 0-1).enrollment will be completed with 350 randomized patients. neurological deficit will be scored with nih stroke scale at day 7 or discharge, or transfer to another hospital, whichever occurs first.patient's clinical condition will be again evaluated by a telephone call after 90 days.

Eligibility criteria:
inclusion criteria: * sudden focal neurological deficit attributable to a stroke * clearly defined time of onset, allowing initiation of intravenous treatment within 3 hours of symptoms onset and intra-arterial treatment within 6 hour of symptoms onset. * age greater than 18 years exclusion criteria: * disability preceding stroke consistent with a modified rankin scale score of 2-4 * coma at onset * rapidly improving neurological deficit * seizure at onset * clinical presentation suggestive of a subarachnoid hemorrhage * previous history of intracranial hemorrhage * septic embolism * arterial puncture at a non compressible site within the previous 7 days * any traumatic brain injury within the previous 14 days * surgery of the central nervous system in the previous 3 months * gastrointestinal hemorrhage or urinary tract hemorrhage within the previous 14 days. * current therapy with intravenous or subcutaneous heparin to rise the clotting time * known hereditary or acquired hemorrhagic diathesis, baseline inr greater than 1.5, aptt more than 1.5 times normal, or baseline platelet count less than 100,000 per cubic millimeter * baseline blood glucose concentrations below 2.75 mm/l (50 mg/dl). * known contrast sensitivity. * women of childbearing potential (unless pregnancy impossible) or known to be breastfeeding. uncontrolled hypertension defined by a blood pressure greater or equal 185 mmhg systolic or diastolic greater or equal 110 mm hg in 3 separate occasions at least 10 minutes apart or requiring continuous iv therapy. * prognosis very poor regardless of therapy; likely to be dead within months. * unlikely to be available for follow-up (eg, no fixed home address, visitor from overseas). * any other condition which local investigators feels would pose a significant hazard in terms of risk/benefit to the patient, or if therapies are impracticable. computed tomographic (ct) scan exclusion criteria * intracranial tumors except small meningioma * hemorrhage of any degree * acute infarction (since this may be an indicator that the time of onset is uncorrected)

Keywords: acute ischemic stroke thrombolysis intra-arterial thrombolysis