To assess the effect of IAT compared with best medical treatment in patients with AIS caused by an intracranial large vessel occlusion of the anterior circulation, who have moderate to good collaterals and who can be treated between 6 and 24 hours…
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is the score on the mRS 90 days after inclusion in the
study. The primary effect parameter should take the whole range of the mRS into
account and is defined as the relative risk for improvement on the mRS
estimated as a common odds ratio with ordinal logistic regression.
Multivariable regression analysis will be used to adjust for chance imbalances
in main prognostic variables between the intervention and control group, such
as age, stroke severity (NIHSS), time since onset, previous stroke, atrial
fibrillation and diabetes mellitus.
Secondary outcome
Secondary outcomes include hemorrhage and stroke severity at 24 hours and 5-7
days, recanalization on CTA at 24 hours or MRA at 24-48 hours and when chosen
for CTA at 24 hours; infarct size at 5-7 days on non-contrast CT will follow.
Background summary
Rationale: Intra-arterial treatment (IAT) by means of retrievable stents, in
patients with acute ischemic stroke (AIS) in the anterior circulation with
confirmed proximal intracranial occlusion, in whom the procedure can be started
within 6 hours from onset has been proven safe and effective. Unfortunately a
large proportion of patients presents beyond the 6 hours timewindow. In the
Netherlands up to 25% of acute ischemic stroke patients arrive in the hospital
between 6 and 12 hours after symptom onset. Currently, only for a very select
group of patients a proven effective recanalization therapy is available. DAWN
and DEFUSE3 randomised patients for IAT or no-IAT in the late timewindow based
on strict CT perfusion characteristics. They proved that IAT is effective for a
very select group and that advanced imaging is requiered for the selection of
these patients. In the ESCAPE trial, one of the recent trials which showed
efficacy of IAT, patients were randomized in the 0 to 12 hours time window.
Patients were selected by NCCT and CT angiography. Eligible patients needed to
have a small core infarct defined as an ASPECTS score of >5, and a moderate to
good collateral flow on CT angiography in addition to a proven the proximal
intracranial anterior circulation occlusion. Of all recent trials, IAT was most
effective in this selected population. Most patients were treated within 6
hours from symptom onset, whereasand only a small proportion was treated
between 6 and 12 hours after symptom onset. The effect size in patients treated
beyond 6 hours was the same as in the early treated group. However, this
predefined subgroup was too small to draw firm conclusions. In pre-defined
subgroup analyses of the MR CLEAN study we showed that of these two imaging
parameters (ASPECTS score and collateral flow) only the degree of collateral
flow showed an interaction with effect of intra-arterial treatment. We
hypothesize that IAT is not only effective for patients treated within 6 hours,
but also for patients selected on the presence of collateral flow treated
between 6 and 24 hours after symptom onset or last seen well less than 24 hours
before admission to the hospital (what also includes wake up strokes)
Study objective
To assess the effect of IAT compared with best medical treatment in patients
with AIS caused by an intracranial large vessel occlusion of the anterior
circulation, who have moderate to good collaterals and who can be treated
between 6 and 24 hours after symptom onset or last seen well less than 24 hours
before admission to the hospital (what also includes wake up strokes). We
expect to demonstrate at least 10% difference in outcome in favor of
endovascular treatment.
Study design
This is a multicenter clinical trial with randomized treatment allocation, open
label treatment and blinded endpoint evaluation (PROBE design).
The intervention contrast is endovascular treatment versus no endovascular
treatment. The treatment is provided in addition to best medical management.
Intervention
The intervention group will receive IAT with a stent retriever or other device
approved by the steering committee. The control group will receive best medical
treatment.
Study burden and risks
All patients in the intervention group will be transferred to the angiosuite.
The procedure involves catheterization according to the Seldinger method, with
a small risk of groin hematoma and dissection. Also, thrombectomy is associated
with cerebral infarction at a distal side. Thrombectomy is of potential
benefit. At three months, all patients will be interviewed to assess functional
outcome.
Every participant will undergo 24 hours after randomization a CTA of the
cerebral vessels to asses rate of recanalization and 5 - 7 days after
randimization a CT brain to assess final infarct volume.Three months after
inclusion all participants will be interviewed by telephone to determine final
oiutcome. This call will take 15 minutes.
In the 5 IAT trials the risk for extra- and intracranieal hemmorrhage was equal
in both arms. This accounted also for post-procedural complications.
The overall risk for procedure-related complications was very low.
Thrombectomy might be of potential benefit outweighting this risks.
P Debeijelaan 25
Maastricht 6229HX
NL
P Debeijelaan 25
Maastricht 6229HX
NL
Listed location countries
Age
Inclusion criteria
o clinical diagnosis of acute ischemic stroke,
o caused by proximal intracranial anterior circulation occlusion (distal
intracranial carotid artery or middle (M1/M2 ) cerebral artery confirmed by
neuro-imaging (CTA),
o and presence of poor*, moderate or good collateral flow as shown by
neuro-imaging (CTA)
o CT or MRI ruling out intracranial hemorrhage,
o Start of IA treatment (groin puncture) possible between 6 and 24 hours or
last seen well < 24 hours including wake-up strokes,
o a score of at least 2 on the NIH Stroke Scale
o age of 18 years or older
o Written informed consent (deferred)
* Inclusion and randomization will be restricted to patients with moderate or
good collaterals when 100 patients with poor collaterals have been included in
the study.
Exclusion criteria
o Pre-stroke disability which interferes with the assessment of functional
outcome at 90 days, i.e. mRS >2
o cerebral infarction in the previous 6 weeks with residual neurological
deficit or signs of recent infarction on neuroimaging in the territory of the
middle cerebral artery
o INR exceeding 3.0*
o platelet count < 40 x 109/L*
o APTT > 50 sec*
o visible infarction in > 1/3 of the territory of the middle cerebral artery
o participation in trials other than current and MR ASAP.
o ICA-T/M1 occlusion, NIHSS >=10, infarct core <=25ml and a mismatch ratio total
ischemic volume/ infarct core >=2 (patient is eligible for direct EVT treatment,
based on DAWN/DEFUSE 3 patient profile)
Inclusion in other intervention trials during the study period is not allowed
* In case there is no clinical indication to test for hemorrhagic diathesis, it
may be assumed that the INR, APTT and platelet count are within these limits.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL58246.078.17 |