StrokePhase 3NCT00540527
Local Versus Systemic Thrombolysis for Acute Ischemic Stroke (SYNTHESIS)
A Phase 3 study testing local interarterial recombinant tissue plasminogen activator and intravenous (IV) rt-PA in people with Stroke and Cerebrovascular Accident, run by Niguarda Hospital at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Stroke, Cerebrovascular Accident
- What is being tested?
- local interarterial recombinant tissue plasminogen activator and intravenous (IV) rt-PA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteItaly
- Study dates
- Jan 2004to Jan 2008
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 30Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: SYNTHESIS: a Randomized Controlled Trial on Intra-arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke. Start up Phase.
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.
Read the 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.
- Conditions
- Stroke, Cerebrovascular Accident
- Being tested
- local interarterial recombinant tissue plasminogen activator, intravenous (IV) rt-PA
- Keywords
- acute ischemic stroke;thrombolysis;intraarterial thrombolysis
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
local interarterial recombinant tissue plasminogen activatorDrug
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
intravenous (IV) rt-PADrug
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
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | local intraarterial recombinant tissue plasminogen activator Receives: Drug: local interarterial recombinant tissue plasminogen activator |
| 2 | Active comparator | intravenous (IV) rt-PA Receives: Drug: intravenous (IV) rt-PA |
What is being measured
The primary outcome is the main question the study is designed to answer.
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) .
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2007 (estimated)
- Study startJan 2004
- Primary completionJan 2008
- Study completionJan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Niguarda Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alfonso Ciccone, MD, Principal investigator, Azienda Ospedaliera Ospedale Niguarda Ca' Granda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00540527
- Sponsor's protocol ID
- SYNTHESIS
- Status last verified
- Oct 2012
- First submitted
- 5 Oct 2007
- Last updated
- 26 Oct 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 21990564
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SYNTHESIS: a Randomized Controlled Trial on Intra-arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke. Start up Phase.
- ClinicalTrials.gov ID
- NCT00540527
- Acronym / sponsor ID
- SYNTHESIS
- Conditions
- Stroke, Cerebrovascular Accident
- Keywords
- acute ischemic stroke;thrombolysis;intraarterial thrombolysis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Niguarda HospitalUniversity, hospital or other
- Study start
- Jan 2004
- Primary completion
- Jan 2008 (actual)
- Study completion
- Jan 2008 (actual)
- First posted
- 8 Oct 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: local interarterial recombinant tissue plasminogen activatorlocal intraarterial recombinant tissue plasminogen activator |
| 2 | Active comparator | Drug: intravenous (IV) rt-PAintravenous (IV) rt-PA |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (30 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| local interarterial recombinant tissue plasminogen activatorEndovascular 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 | Drug | 1 |
| intravenous (IV) rt-PAIV 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 | Drug | 2 |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2012.
- Results publication: PubMed 21990564Ciccone 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alfonso Ciccone, MD principal investigator
Azienda Ospedaliera Ospedale Niguarda Ca' Granda
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing local interarterial recombinant tissue plasminogen activator and intravenous (IV) rt-PA in people with Stroke and Cerebrovascular Accident, run by Niguarda Hospital at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00540527, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2012.