Intra-arterial Versus Systemic Thrombolysis for Acute Ischemic Stroke

Stroke Clinical Trial

— SYNTHESIS EXP  

Official title:

Synthesis Expansion: A Randomized Controlled Trial on Intra-Arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00640367
• Other study ID #: SYNTHESIS EXPANSION
• Status: Completed
• Phase: Phase 3
• First received: March 18, 2008
• Last updated: April 24, 2014
• Start date: February 2008
• Est. completion date: July 2012

Study information

• Verified date: April 2014
• Source: Niguarda Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 350
• Est. completion date: July 2012
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cerebrovascular Accident
• Stroke

Intervention

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

Locations

Country	Name	City	State
Italy	A.O. Ospedale Ca' Granda	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Niguarda Hospital

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		3 months	No
Secondary	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		7 days	Yes