Intra-arterial Versus Systemic Thrombolysis for Acute Ischemic Stroke - Full Text View

Sponsor:	Niguarda Hospital
Information provided by:	Niguarda Hospital
ClinicalTrials.gov Identifier:	NCT00640367

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 III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Synthesis Expansion: A Randomized Controlled Trial on Intra-Arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke

Resource links provided by NLM:

Drug Information available for: Alteplase Tissue-type plasminogen activator

U.S. FDA Resources

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 ]

Estimated Enrollment:	350
Study Start Date:	February 2008
Estimated Study Completion Date:	August 2010
Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
IA thrombolysis: Experimental 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
IV rtPA: Active Comparator 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

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

Contacts

Contact: Alfonso Ciccone, MD

+39 02 6444 ext 2348

alfonso.ciccone@ospedaleniguarda.it

Locations

Italy
A.O. Ospedale Ca' Granda	Recruiting
Milan, Italy, 20162
Principal Investigator: Alfonso CIccone, MD

Sponsors and Collaborators

Niguarda Hospital

Investigators

Principal Investigator:

Alfonso Ciccone, MD

A.O. Ospedale Niguarda Ca' Granda

More Information

Additional Information:

web site

This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	A.O. Ospedale Niguarda Ca' Granda - Milano ( Alfonso Ciccone, MD )
Study ID Numbers:	SYNTHESIS EXPANSION
Study First Received:	March 18, 2008
Last Updated:	September 17, 2009
ClinicalTrials.gov Identifier:	NCT00640367 History of Changes
Health Authority:	Italy: Ministry of Health

Keywords provided by Niguarda Hospital:

Acute ischemic stroke
thrombolysis
intra-arterial thrombolysis

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Cerebral Infarction
Hematologic Agents
Stroke
Nervous System Diseases
Vascular Diseases
Central Nervous System Diseases
Tissue Plasminogen Activator
Fibrinolytic Agents

Cardiovascular Agents
Brain Diseases
Cerebrovascular Disorders
Pharmacologic Actions
Fibrin Modulating Agents
Therapeutic Uses
Brain Ischemia
Cardiovascular Diseases
Brain Infarction

ClinicalTrials.gov processed this record on February 08, 2010