Back to results

Local Versus Systemic Thrombolysis for Acute Ischemic Stroke (SYNTHESIS)

Primary Purpose

Stroke, Cerebrovascular Accident

Status

Completed

Phase

Phase 3

Locations

Italy

Study Type

Interventional

Intervention

local interarterial recombinant tissue plasminogen activator

intravenous (IV) rt-PA

About this trial

This is an interventional treatment trial for Stroke focused on measuring acute ischemic stroke;thrombolysis;intraarterial 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 between 18 and 80 years

Exclusion criteria:

Disability preceding stroke consistent with a modified Rankin scale score of 2-4 (see glossary for Rankin scale)
Coma at onset
Severe stroke as assessed clinically (e.g. NIHSS>25)
Rapidly improving neurological deficit or minor symptoms
Seizure at onset of stroke
Clinical presentation suggestive of a subarachnoid hemorrhage (even of CT scan is normal) or condition after subarachnoid hemorrhage from aneurysm
Previous history of or suspected intracranial hemorrhage
Previous history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery)
Septic embolism, bacterial endocarditis, pericarditis
Acute pancreatitis
Arterial puncture at a non compressible site (e.g. subclavian or jugular vein puncture) or traumatic external heart massage or obstetrical delivery within the previous 10 days
Another stroke or serious head trauma within the preceding 3 months
Major surgery or significant trauma in past 3 month
Urinary tract hemorrhage within the previous 21 days
Documented ulcerative gastrointestinal disease during the last 3 months, esophageal varices, arterial-aneurysm, arterial/venous malformations • Neoplasm with increased bleeding risk
Severe liver disease, including hepatic failure, cirrhosis, portal hypertension (esophageal varices) and active hepatitis
Current therapy with intravenous or subcutaneous heparin or oral anticoagulants (e.g. warfarin sodium) 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 50 mg per deciliter (2.75 mm/L) or above 400 mg per deciliter
Hemorrhagic retinopathy, e.g. in diabetes (vision disturbances may indicate hemorrhagic retinopathy)
Any history of prior stroke and concomitant diabetes
Prior stroke within the last 3 months
Known contrast sensitivity
Severe uncontrolled hypertension defined by a blood pressure ≥ 185 mmHg systolic or diastolic ≥ 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 (e.g., 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

AO Ospedale Niguarda Ca' Granda

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm Description

local intraarterial recombinant tissue plasminogen activator

intravenous (IV) rt-PA

Outcomes

Primary Outcome Measures

To assess whether local intra-arterial (LIA) recombinant tissue plasminogen activator rt-PA, as compared to intravenous (IV) rt-PA, increases survival free of disability (modified Rankin score of 0 or 1) .

Secondary Outcome Measures

Full Information

NCT ID

NCT00540527

First Posted

October 5, 2007

Last Updated

October 24, 2012

Sponsor

Niguarda Hospital

1. Study Identification

Unique Protocol Identification Number

NCT00540527

Brief Title

Local Versus Systemic Thrombolysis for Acute Ischemic Stroke (SYNTHESIS)

Official Title

SYNTHESIS: a Randomized Controlled Trial on Intra-arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke. Start up Phase.

Study Type

Interventional

2. Study Status

Record Verification Date

October 2012

Overall Recruitment Status

Completed

Study Start Date

January 2004 (undefined)

Primary Completion Date

January 2008 (Actual)

Study Completion Date

January 2008 (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

The purpose of this study is to determine whether intra-arterial rt-PA within 6 hours from an ischemic stroke onset, compared with intravenous infusion of the same drug within 3 hours, increases the proportion of independent survivors at 3 months.

Detailed Description

"Stroke is a major cause of death and severe disability.The only effective, available therapy, within few hours of stroke onset, is rt-PA, a thrombolytic agent. Preliminary experience but not from properly conducted randomized trials indicates that intra-arterial treatment might be more effective than intravenous therapy for some vascular lesions. Intravenous application has not been tested directly against intra-arterial treatment and we do not known the relative clinical effectiveness with these two routes of administration. Eligible patients will be randomized to receive either IV rt-PA (0.9mg/kg; max 90 mg), 10% of which would be infused over 1 minute, and the remainder over 60 min, or IA rt-PA within the thrombus by means of microcatheter. In patients allocated to IA rt-PA the angiogram is performed as soon as possible within 6 hours of stroke onset; IV heparin has to be initiated (2000 U bolus followed by 500 U7hr infusion) and rt-PA is delivered at a rate of about 90 mg/hr for maximum one hour at the dose needed for recanalization up to 0.9 mg/Kg (max 90 mg). Antithrombotics and anticoagulants are disallowed during the first 24 hours (except heparin used during the angiogram). After 24 hrs, all patients will be considered for long-term antiplatelet or anticoagulant therapy. Follow-up will take place at 7 days, discharge, or transfer, whichever is first; and again at 3 months. 4 centers are currently authorized for the start-up phase; 15 centers in Italy have applied for an expansion phase of the study (SYNTHESIS EXPANSION), with financial support from Italian National Agency for Drugs (AIFA).The two phases of the study will be analysed separately and will be considered in a pooled analysis.

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;intraarterial thrombolysis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

54 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

local intraarterial recombinant tissue plasminogen activator

Arm Title

Arm Type

Active Comparator

Arm Description

intravenous (IV) rt-PA

Intervention Type

Drug

Intervention Name(s)

local interarterial recombinant tissue plasminogen activator

Intervention Description

Endovascular treatment must be performed asap after random.and definitely within 6h from symp. onset.It includes intrarterial thrombolysis with rt-PA,if necessary,associated to or substituted by mechanical clot disruption and/or retrieval.Fibrinolytic therapy should be performed within 1h,the full dose of rt-PA infusion should not exceed 0.9 mg/kg (max 90 mg in the case of body weight ≥100 kg).If a complete recanalization is achieved,rt-PA infusion can be interrupted before reaching the maximum dosage.The option of performing a thrombolysis by mechanical means to obtain a mechanical disintegration/shift/detach/fissure of the thrombus and/or a retraction/aspiration can be considered on the basis of the type,location and characteristics of the occlusion.These choices may involve the use of the microguidewire as a mechanical instrument to favour the disintegration of the thrombus,using systems to capture the thrombus by extraction or more complex systems to crush and aspirate the thrombus

Intervention Type

Drug

Intervention Name(s)

intravenous (IV) rt-PA

Intervention Description

IV thrombolytic treatment is started immediately after randomization, within 4.5 h of symptoms onset. IV rt-PA is administered at a dose of 0.9 mg/kg (max 90 mg), 10% of which is given as a bolus, followed by the delivery of the remaining 90% as a constant infusion over 60 mins

Primary Outcome Measure Information:

Title

Time Frame

3 months

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 between 18 and 80 years Exclusion criteria: Disability preceding stroke consistent with a modified Rankin scale score of 2-4 (see glossary for Rankin scale) Coma at onset Severe stroke as assessed clinically (e.g. NIHSS>25) Rapidly improving neurological deficit or minor symptoms Seizure at onset of stroke Clinical presentation suggestive of a subarachnoid hemorrhage (even of CT scan is normal) or condition after subarachnoid hemorrhage from aneurysm Previous history of or suspected intracranial hemorrhage Previous history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery) Septic embolism, bacterial endocarditis, pericarditis Acute pancreatitis Arterial puncture at a non compressible site (e.g. subclavian or jugular vein puncture) or traumatic external heart massage or obstetrical delivery within the previous 10 days Another stroke or serious head trauma within the preceding 3 months Major surgery or significant trauma in past 3 month Urinary tract hemorrhage within the previous 21 days Documented ulcerative gastrointestinal disease during the last 3 months, esophageal varices, arterial-aneurysm, arterial/venous malformations • Neoplasm with increased bleeding risk Severe liver disease, including hepatic failure, cirrhosis, portal hypertension (esophageal varices) and active hepatitis Current therapy with intravenous or subcutaneous heparin or oral anticoagulants (e.g. warfarin sodium) 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 50 mg per deciliter (2.75 mm/L) or above 400 mg per deciliter Hemorrhagic retinopathy, e.g. in diabetes (vision disturbances may indicate hemorrhagic retinopathy) Any history of prior stroke and concomitant diabetes Prior stroke within the last 3 months Known contrast sensitivity Severe uncontrolled hypertension defined by a blood pressure ≥ 185 mmHg systolic or diastolic ≥ 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 (e.g., 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

Azienda Ospedaliera Ospedale Niguarda Ca' Granda

Official's Role

Principal Investigator

Facility Information:

Facility Name

AO Ospedale Niguarda Ca' Granda

City

Milan

ZIP/Postal Code

20162

Country

Italy

12. IPD Sharing Statement

Citations:

PubMed Identifier

21990564

Citation

Ciccone A, Valvassori L, Ponzio M, Ballabio E, Gasparotti R, Sessa M, Scomazzoni F, Tiraboschi P, Sterzi R; SYNTHESIS Investigators. Intra-arterial or intravenous thrombolysis for acute ischemic stroke? The SYNTHESIS pilot trial. J Neurointerv Surg. 2010 Mar;2(1):74-9. doi: 10.1136/jnis.2009.001388. Epub 2009 Oct 30.

Results Reference

result

Learn more about this trial

Local Versus Systemic Thrombolysis for Acute Ischemic Stroke (SYNTHESIS)

We'll reach out to this number within 24 hrs