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

Niguarda Hospital

Status and phase

Completed

Phase 3

Conditions

Cerebrovascular Accident

Stroke

Treatments

Other: Alteplase IA and/or mechanical thrombolysis

Drug: Alteplase IV

Study type

Interventional

Funder types

Other

Identifiers

NCT00640367

SYNTHESIS EXPANSION

Details and patient eligibility

About

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.

Full 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.

Enrollment

350 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

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)