Intra-arterial Versus Systemic Thrombolysis for Acute Ischemic Stroke
Information source: Niguarda Hospital
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Stroke; Cerebrovascular Accident
Intervention: Alteplase IA and/or mechanical thrombolysis (Other); Alteplase IV (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: Niguarda Hospital Official(s) and/or principal investigator(s):
Alfonso Ciccone, MD, Principal Investigator, Affiliation: A.O. Ospedale Niguarda Ca' Granda
Overall contact:
Alfonso Ciccone, MD, Phone: +39 02 6444, Ext: 2348, Email: alfonso.ciccone@ospedaleniguarda.it
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.
Clinical Details
Official title: Synthesis Expansion: A Randomized Controlled Trial on Intra-Arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke
Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: 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.
Secondary outcome: 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
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
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
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)
Locations and Contacts
Alfonso Ciccone, MD, Phone: +39 02 6444, Ext: 2348, Email: alfonso.ciccone@ospedaleniguarda.it
A.O. Ospedale Ca' Granda, Milan 20162, Italy; Recruiting
Alfonso CIccone, MD, Principal Investigator
Additional Information
web site
Starting date: February 2008
Ending date: August 2010
Last updated: September 17, 2009
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