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.
- IV rt-PA Drug
Other Names: Alteplase, Activase Intervention Desc: Thrombolytic
- IA rt-PA Drug
Intervention Desc: Intra-Arterial
- Alteplase IA and/or mechanical thrombolysis Other
Intervention Desc: loca intra-arterial recombinant tissue plasminogen activator and/or mechanical thrombolysis ARM 1: Kind: Experimental Label: IA thrombolysis Description: IA recombinant tissue plasminogen activator and/or mechanical thrombolysis
- Alteplase IV Drug
Intervention Desc: intravenous recombinant tissue plasminogen activator ARM 1: Kind: Experimental Label: IV rtPA Description: IV recombinant tissue plasminogen activator
- Allocation: Randomized
- Masking: Open Label
- Purpose: Treatment
- Endpoint: Safety/Efficacy Study
- Intervention: Parallel Assignment
Eligible patients are randomized to receive either 0.9 mg/kg (max 90 mg) IV tPA (control arm) or up to 0.9 mg/Kg IA tPA (max 90 mg) over 60 minutes locally administered to the thrombus with or without mechanical disaggregation/dislocation or retraction/aspiration. Heparin may be administered in the IA arm, but will not be administered in the IV arm. Neurological deficit will be scored with NIH Stroke Scale at day 7 or day of discharge, whichever occurs first. Patient's clinical condition will be again evaluated by a telephone call after 90 days.
|Type||Measure||Time Frame||Safety Issue|
|Primary||To assess whether local IA tPA, as compared to IV tPA, increases survival free of disability (modified Rankin score 0-1) at 3 months.|
|Secondary||1. To assess whether IA tPA versus IV tPA improves the 7 day neurological deficit. 2. To assess the safety of IA tPA versus IV tPA with respect to symptomatic intracranial hemorrhage, fatal and non-fatal stroke, death from any cause, and neurological deterioration within 7 days.|
|Primary||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||No|
|Secondary||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||Yes|
- Niguarda Hospital Lead