Local Versus Systemic Thrombolysis for Acute Ischemic Stroke (SYNTHESIS)
Condition: Stroke; Cerebrovascular Accident
MeSH terms: Stroke; Ischemic Stroke
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to determine whether intra-arterial rt-PA within 6 hours from an
      ischemic stroke onset, compared with intravenous infusion of the same drug within 3 hours,
      increases the proportion of independent survivors at 3 months.
    

Detailed description: 
      "Stroke is a major cause of death and severe disability.The only effective, available
      therapy, within few hours of stroke onset, is rt-PA, a thrombolytic agent. Preliminary
      experience but not from properly conducted randomized trials indicates that intra-arterial
      treatment might be more effective than intravenous therapy for some vascular lesions.
      Intravenous application has not been tested directly against intra-arterial treatment and we
      do not known the relative clinical effectiveness with these two routes of administration.
      Eligible patients will be randomized to receive either IV rt-PA (0.9mg/kg; max 90 mg), 10% of
      which would be infused over 1 minute, and the remainder over 60 min, or IA rt-PA within the
      thrombus by means of microcatheter. In patients allocated to IA rt-PA the angiogram is
      performed as soon as possible within 6 hours of stroke onset; IV heparin has to be initiated
      (2000 U bolus followed by 500 U7hr infusion) and rt-PA is delivered at a rate of about 90
      mg/hr for maximum one hour at the dose needed for recanalization up to 0.9 mg/Kg (max 90 mg).
      Antithrombotics and anticoagulants are disallowed during the first 24 hours (except heparin
      used during the angiogram). After 24 hrs, all patients will be considered for long-term
      antiplatelet or anticoagulant therapy. Follow-up will take place at 7 days, discharge, or
      transfer, whichever is first; and again at 3 months. 4 centers are currently authorized for
      the start-up phase; 15 centers in Italy have applied for an expansion phase of the study
      (SYNTHESIS EXPANSION), with financial support from Italian National Agency for Drugs
      (AIFA).The two phases of the study will be analysed separately and will be considered in a
      pooled analysis.
    

Intervention name(s): local interarterial recombinant tissue plasminogen activator; intravenous (IV) rt-PA
Intervention type(s): Drug; Drug
Intervention description(s): Endovascular treatment must be performed asap after random.and definitely within 6h from symp. onset.It includes intrarterial thrombolysis with rt-PA,if necessary,associated to or substituted by mechanical clot disruption and/or retrieval.Fibrinolytic therapy should be performed within 1h,the full dose of rt-PA infusion should not exceed 0.9 mg/kg (max 90 mg in the case of body weight ≥100 kg).If a complete recanalization is achieved,rt-PA infusion can be interrupted before reaching the maximum dosage.The option of performing a thrombolysis by mechanical means to obtain a mechanical disintegration/shift/detach/fissure of the thrombus and/or a retraction/aspiration can be considered on the basis of the type,location and characteristics of the occlusion.These choices may involve the use of the microguidewire as a mechanical instrument to favour the disintegration of the thrombus,using systems to capture the thrombus by extraction or more complex systems to crush and aspirate the thrombus; IV thrombolytic treatment is started immediately after randomization, within 4.5 h of symptoms onset. IV rt-PA is administered at a dose of 0.9 mg/kg (max 90 mg), 10% of which is given as a bolus, followed by the delivery of the remaining 90% as a constant infusion over 60 mins
Intervention MeSH terms: Plasminogen; Tissue Plasminogen Activator
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: acute ischemic stroke;thrombolysis;intraarterial thrombolysis