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

Tracking Information
First Submitted Date ICMJE	March 18, 2008
First Posted Date ICMJE	March 21, 2008
Last Update Posted Date	April 25, 2014
Study Start Date ICMJE	February 2008
Actual Primary Completion Date	February 2009 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: March 27, 2008)	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 ]
Original Primary Outcome Measures ICMJE; (submitted: March 18, 2008)	To assess whether local IA r-PA, 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 ]
Change History	Complete list of historical versions of study NCT00640367 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: March 27, 2008)	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 ]
Original Secondary Outcome Measures ICMJE; (submitted: March 18, 2008)	1. IA rt-PA vs.IV rt-PA improves the 7 day neurological deficit. 2. IA rt-PA vs.IV rt-PA 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 ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Intra-arterial Versus Systemic Thrombolysis for Acute Ischemic Stroke
Official Title ICMJE	Synthesis Expansion: A Randomized Controlled Trial on Intra-Arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke
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.
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.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Stroke; Cerebrovascular Accident
Intervention ICMJE	Other: Alteplase IA and/or mechanical thrombolysis loca intra-arterial recombinant tissue plasminogen activator and/or mechanical thrombolysis; Drug: Alteplase IV intravenous recombinant tissue plasminogen activator
Study Arms	Experimental: IA thrombolysis IA recombinant tissue plasminogen activator and/or mechanical thrombolysis Intervention: Other: Alteplase IA and/or mechanical thrombolysis; Active Comparator: IV rtPA IV recombinant tissue plasminogen activator Intervention: Drug: Alteplase IV
Publications *	Ciccone A, Valvassori L, Nichelatti M, Sgoifo A, Ponzio M, Sterzi R, Boccardi E; SYNTHESIS Expansion Investigators. Endovascular treatment for acute ischemic stroke. N Engl J Med. 2013 Mar 7;368(10):904-13. doi: 10.1056/NEJMoa1213701. Epub 2013 Feb 6.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: March 18, 2008)	350
Original Estimated Enrollment ICMJE	Same as current
Actual Study Completion Date	July 2012
Actual Primary Completion Date	February 2009 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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)
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 80 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Italy
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00640367
Other Study ID Numbers ICMJE	SYNTHESIS EXPANSION
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Niguarda Hospital
Study Sponsor ICMJE	Niguarda Hospital
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Alfonso Ciccone, MD A.O. Ospedale Niguarda Ca' Granda
PRS Account	Niguarda Hospital
Verification Date	April 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP