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

Primary Purpose

Stroke, Cerebrovascular Accident

Status

Completed

Phase

Phase 3

Locations

Italy

Study Type

Interventional

Intervention

Alteplase IA and/or mechanical thrombolysis

Alteplase IV

About this trial

This is an interventional treatment trial for Stroke focused on measuring Acute ischemic stroke, thrombolysis, intra-arterial thrombolysis

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

A.O. Ospedale Ca' Granda

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

IA thrombolysis

IV rtPA

Arm Description

IA recombinant tissue plasminogen activator and/or mechanical thrombolysis

IV recombinant tissue plasminogen activator

Outcomes

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.

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

Full Information

NCT ID

NCT00640367

First Posted

March 18, 2008

Last Updated

April 24, 2014

Sponsor

Niguarda Hospital

1. Study Identification

Unique Protocol Identification Number

NCT00640367

Brief Title

Intra-arterial Versus Systemic Thrombolysis for Acute Ischemic Stroke

Acronym

SYNTHESIS EXP

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2014

Overall Recruitment Status

Completed

Study Start Date

February 2008 (undefined)

Primary Completion Date

February 2009 (Actual)

Study Completion Date

July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Niguarda Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Stroke, Cerebrovascular Accident

Keywords

Acute ischemic stroke, thrombolysis, intra-arterial thrombolysis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

350 (Actual)

8. Arms, Groups, and Interventions

Arm Title

IA thrombolysis

Arm Type

Experimental

Arm Description

IA recombinant tissue plasminogen activator and/or mechanical thrombolysis

Arm Title

IV rtPA

Arm Type

Active Comparator

Arm Description

IV recombinant tissue plasminogen activator

Intervention Type

Other

Intervention Name(s)

Alteplase IA and/or mechanical thrombolysis

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Alteplase IV

Intervention Description

intravenous recombinant tissue plasminogen activator

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

Time Frame

7 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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. 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alfonso Ciccone, MD

Organizational Affiliation

A.O. Ospedale Niguarda Ca' Granda

Official's Role

Principal Investigator

Facility Information:

Facility Name

A.O. Ospedale Ca' Granda

City

Milan

ZIP/Postal Code

20162

Country

Italy

12. IPD Sharing Statement

Citations:

PubMed Identifier

23387822

Citation

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.

Results Reference

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Intra-arterial Versus Systemic Thrombolysis for Acute Ischemic Stroke

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