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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Niguarda Hospital
ClinicalTrials.gov Identifier:
NCT00640367
First received: March 18, 2008
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Synthesis Expansion: A Randomized Controlled Trial on Intra-Arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke

Resource links provided by NLM:


Further study details as provided by Niguarda Hospital:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 350
Study Start Date: February 2008
Study Completion Date: July 2012
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 EXCLUSION CRITERIA

  • Intracranial tumors except small meningioma
  • Hemorrhage of any degree
  • Acute infarction (since this may be an indicator that the time of onset is uncorrected)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00640367

Locations
Italy
A.O. Ospedale Ca' Granda
Milan, Italy, 20162
Sponsors and Collaborators
Niguarda Hospital
Investigators
Principal Investigator: Alfonso Ciccone, MD A.O. Ospedale Niguarda Ca' Granda
  More Information

Additional Information:
No publications provided by Niguarda Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Niguarda Hospital
ClinicalTrials.gov Identifier: NCT00640367     History of Changes
Other Study ID Numbers: SYNTHESIS EXPANSION
Study First Received: March 18, 2008
Last Updated: April 24, 2014
Health Authority: Italy: Ministry of Health

Keywords provided by Niguarda Hospital:
Acute ischemic stroke
thrombolysis
intra-arterial thrombolysis

Additional relevant MeSH terms:
Cerebral Infarction
Stroke
Brain Diseases
Brain Infarction
Brain Ischemia
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Nervous System Diseases
Vascular Diseases
Plasminogen
Tissue Plasminogen Activator
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014