Local Versus Systemic Thrombolysis for Acute Ischemic Stroke (SYNTHESIS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Niguarda Hospital
ClinicalTrials.gov Identifier:
NCT00540527
First received: October 5, 2007
Last updated: October 24, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Stroke
Cerebrovascular Accident
Drug: local interarterial recombinant tissue plasminogen activator
Drug: intravenous (IV) rt-PA
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: SYNTHESIS: a Randomized Controlled Trial on Intra-arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke. Start up Phase.

Resource links provided by NLM:


Further study details as provided by Niguarda Hospital:

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) . [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Enrollment: 54
Study Start Date: January 2004
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
local intraarterial recombinant tissue plasminogen activator
Drug: local interarterial recombinant tissue plasminogen activator
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
Active Comparator: 2
intravenous (IV) rt-PA
Drug: intravenous (IV) rt-PA
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00540527

Locations
Italy
AO Ospedale Niguarda Ca' Granda
Milan, Italy, 20162
Sponsors and Collaborators
Niguarda Hospital
Investigators
Principal Investigator: Alfonso Ciccone, MD Azienda Ospedaliera Ospedale Niguarda Ca' Granda
  More Information

Additional Information:
Publications:
Responsible Party: Niguarda Hospital
ClinicalTrials.gov Identifier: NCT00540527     History of Changes
Other Study ID Numbers: SYNTHESIS
Study First Received: October 5, 2007
Last Updated: October 24, 2012
Health Authority: Italy: Ministry of Health

Keywords provided by Niguarda Hospital:
acute ischemic stroke;thrombolysis;intraarterial thrombolysis

Additional relevant MeSH terms:
Stroke
Cerebral Infarction
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Plasminogen
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on September 18, 2014