Intra-arterial Versus Systemic Thrombolysis for Acute Ischemic Stroke

NCT ID: NCT00640367

Last Updated: 2014-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2012-07-31

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.

Conditions

Stroke; Cerebrovascular Accident

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IA thrombolysis

IA recombinant tissue plasminogen activator and/or mechanical thrombolysis

Group Type: EXPERIMENTAL

Alteplase IA and/or mechanical thrombolysis

Intervention Type: OTHER

loca intra-arterial recombinant tissue plasminogen activator and/or mechanical thrombolysis

IV rtPA

IV recombinant tissue plasminogen activator

Group Type: ACTIVE_COMPARATOR

Alteplase IV

Intervention Type: DRUG

intravenous recombinant tissue plasminogen activator

Interventions

Alteplase IA and/or mechanical thrombolysis

loca intra-arterial recombinant tissue plasminogen activator and/or mechanical thrombolysis

Intervention Type: OTHER

Alteplase IV

intravenous recombinant tissue plasminogen activator

Intervention Type: DRUG

Eligibility 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.

• Intracranial tumors except small meningioma
• Hemorrhage of any degree
• Acute infarction (since this may be an indicator that the time of onset is uncorrected)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Niguarda Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alfonso Ciccone, MD

Role: PRINCIPAL_INVESTIGATOR

A.O. Ospedale Niguarda Ca' Granda

Locations

A.O. Ospedale Ca' Granda

Milan, Milan, Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 23387822 (View on PubMed)

Other Identifiers

SYNTHESIS EXPANSION

Identifier Type: -

Identifier Source: org_study_id