StrokePhase 3SYNTHESIS EXPNCT00640367
Intra-arterial Versus Systemic Thrombolysis for Acute Ischemic Stroke
A Phase 3 study testing Alteplase IA and/or mechanical thrombolysis and Alteplase IV in people with Stroke and Cerebrovascular Accident, run by Niguarda Hospital at 1 site in Italy.
Trial 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… 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?
- Alteplase IA and/or mechanical thrombolysis and Alteplase IV
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 350 participants
- Where
- 1 siteItaly
- Study dates
- Feb 2008to Jul 2012
- 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 greater than 18 years
Who cannot join
- 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
Show all 23Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Synthesis Expansion: A Randomized Controlled Trial on Intra-Arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke
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.
Read the 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
- Being tested
- Alteplase IA and/or mechanical thrombolysis, Alteplase IV
- Keywords
- Acute ischemic stroke, thrombolysis, intra-arterial thrombolysis
- Medical subject headings
- Stroke, Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alteplase IA and/or mechanical thrombolysisOther
loca intra-arterial recombinant tissue plasminogen activator and/or mechanical thrombolysis
Alteplase IVDrug
intravenous recombinant tissue plasminogen activator
| Study group | Role | What they receive |
|---|---|---|
| IA thrombolysis | Experimental | IA recombinant tissue plasminogen activator and/or mechanical thrombolysis Receives: Other: Alteplase IA and/or mechanical thrombolysis |
| IV rtPA | Active comparator | IV recombinant tissue plasminogen activator Receives: Drug: Alteplase IV |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 months
Secondary outcomes (1)
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
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2008 (estimated)
- Study startFeb 2008
- Primary completionFeb 2009
- Study completionJul 2012
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
- 350 participants (actual)
Sponsor and investigators
- Lead sponsor
- Niguarda Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alfonso Ciccone, MD, Principal investigator, A.O. Ospedale Niguarda Ca' Granda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00640367
- Sponsor's protocol ID
- SYNTHESIS EXPANSION
- Acronym
- SYNTHESIS EXP
- Status last verified
- Apr 2014
- First submitted
- 18 Mar 2008
- Last updated
- 25 Apr 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 23387822
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Synthesis Expansion: A Randomized Controlled Trial on Intra-Arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke
- ClinicalTrials.gov ID
- NCT00640367
- Acronym / sponsor ID
- SYNTHESIS EXP / SYNTHESIS EXPANSION
- Conditions
- Stroke, Cerebrovascular Accident
- Keywords
- Acute ischemic stroke, thrombolysis, intra-arterial thrombolysis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 350 participants (actual)
- Lead sponsor
- Niguarda HospitalUniversity, hospital or other
- Study start
- Feb 2008
- Primary completion
- Feb 2009 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 21 Mar 2008 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IA thrombolysis | Experimental | Other: Alteplase IA and/or mechanical thrombolysisIA recombinant tissue plasminogen activator and/or mechanical thrombolysis |
| IV rtPA | Active comparator | Drug: Alteplase IVIV recombinant tissue plasminogen activator |
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 greater than 18 years
Key exclusion criteria (23 listed)
- 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
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 |
|---|---|---|
| Alteplase IA and/or mechanical thrombolysisloca intra-arterial recombinant tissue plasminogen activator and/or mechanical thrombolysis | Other | IA thrombolysis |
| Alteplase IVintravenous recombinant tissue plasminogen activator | Drug | IV rtPA |
Primary outcome
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
1 secondary outcome
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
Time frame: 7 days
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 25 Apr 2014.
- Derived from this study: PubMed 23387822Ciccone 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.
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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
A.O. 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 Alteplase IA and/or mechanical thrombolysis and Alteplase IV 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 23 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 25 Apr 2014. 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 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). 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 NCT00640367, 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 25 Apr 2014.