Intra-arterial Versus Systemic Thrombolysis for Acute Ischemic Stroke "SYNTHESIS EXP"

Completed

Phase 3 Results N/A

Trial Description

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.

Conditions

Interventions

  • 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

Trial Design

  • Allocation: Randomized
  • Masking: Open Label
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Patient Involvement

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.

Outcomes

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

Sponsors