Cerebrovascular Accident, Stroke
Conditions
Keywords
Acute ischemic stroke, thrombolysis, intra-arterial thrombolysis
Brief 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.
Detailed description
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.
Interventions
OTHERAlteplase IA and/or mechanical thrombolysis
loca intra-arterial recombinant tissue plasminogen activator and/or mechanical thrombolysis
DRUGAlteplase IV
intravenous recombinant tissue plasminogen activator
Sponsors
Niguarda Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess whether IA thrombolysis, as compared to IV rt-PA, increases survival free of disability (modified Rankin score of zero or 1) at 3 months. | 3 months |
Secondary
| Measure | Time frame |
|---|---|
| To asses whether IA thrombolysis vs.IV rt-PA 1.improves the 7 day neurological deficit; 2.is safe on the base of symptomatic intracranial hemorrhages, fatal and non-fatal stroke, death from any cause, neurological deterioration within 7 days | 7 days |
Countries
Italy
Outcome results
None listed