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

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ClinicalTrials.gov Identifier: NCT00640367
Recruitment Status : Completed
First Posted : March 21, 2008
Last Update Posted : April 25, 2014
Information provided by (Responsible Party):
Niguarda Hospital

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.

Condition or disease Intervention/treatment Phase
Stroke Cerebrovascular Accident Other: Alteplase IA and/or mechanical thrombolysis Drug: Alteplase IV Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 350 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Synthesis Expansion: A Randomized Controlled Trial on Intra-Arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke
Study Start Date : February 2008
Actual Primary Completion Date : February 2009
Actual Study Completion Date : July 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ischemic Stroke
Drug Information available for: Alteplase

Arm Intervention/treatment
Experimental: IA thrombolysis
IA recombinant tissue plasminogen activator and/or mechanical thrombolysis
Other: Alteplase IA and/or mechanical thrombolysis
loca intra-arterial recombinant tissue plasminogen activator and/or mechanical thrombolysis

Active Comparator: IV rtPA
IV recombinant tissue plasminogen activator
Drug: Alteplase IV
intravenous recombinant tissue plasminogen activator

Primary Outcome Measures :
  1. 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. [ Time Frame: 3 months ]

Secondary Outcome Measures :
  1. 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 [ Time Frame: 7 days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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.


  • Intracranial tumors except small meningioma
  • Hemorrhage of any degree
  • Acute infarction (since this may be an indicator that the time of onset is uncorrected)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00640367

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A.O. Ospedale Ca' Granda
Milan, Italy, 20162
Sponsors and Collaborators
Niguarda Hospital
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Principal Investigator: Alfonso Ciccone, MD A.O. Ospedale Niguarda Ca' Granda
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Niguarda Hospital
ClinicalTrials.gov Identifier: NCT00640367    
First Posted: March 21, 2008    Key Record Dates
Last Update Posted: April 25, 2014
Last Verified: April 2014
Keywords provided by Niguarda Hospital:
Acute ischemic stroke
intra-arterial thrombolysis
Additional relevant MeSH terms:
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Ischemic Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action