To assess the effect of acetylsalicylic acid (ASA) and unfractionated heparin, alone, or in combination, in patients with AIS, who undergo IAT for a confirmed intracranial anterior circulation occlusion.
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
- Vascular therapeutic procedures
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is the score on the modified Rankin Scale (mRS) 90 days
after inclusion in the study. The primary effect parameter is defined as the
relative risk for improvement on the mRS estimated as an odds ratio with
ordinal logistic regression. Multivariable regression analysis will be used to
adjust for chance imbalances in main prognostic variables.
Secondary outcome
Secondary outcomes include mortality at 90 days, stroke severity measured with
the National Institutes of Health Stroke Scale (NIHSS) at 24 hours and 5-7
days, recanalization on postprocedural DSA (measured with the extended
treatment in cerebral ischemia (eTICI)) and on CTA at 24 hours +/- 12 hours or
MRA at 24-48 hours and infarct size at 5-7 days, or 24-48 hours when MRI per
performed, and dichotomized mRS, death, score on the EQ5D-5L and Barthel index
at 90 days. In a subset of 600 patients we will assess reperfusion and infarct
size with MRI. Safety endpoints include symptomatic intracerebral hemorrhage.
Tertiary objectives are 1) to collect (waste) biomaterials (including
thrombo-emboli, aspirate blood) and to analyze biofactors in blood samples with
respect to their potential for treatment effect modification, 2) to collect and
analyze data regarding the deferred consent procedure and its association with
patient recall and satisfaction at three months from randomization, and 3) to
study the efficiency of national IAT implementation, given the availability of
IAT hospitals and capacity, and travel times of ambulance services. To this
end, we aim to collect data (time delays and diagnostics) from each step in the
acute stroke pathway as input parameters for a simulation model. This way we
can study the regional set-up of the IAT organizational model.
Other outcome measures are mRS, quality of life score (EQ5D-5L), major vascular
events, health care amount and loss of
productivity measured once at max 36 months after stroke, in patients who were
included in the trial after august 1, 2020.
Background summary
Intra-arterial treatment (IAT) by means of retrievable stents, in patients with
acute ischemic stroke (AIS) with confirmed proximal intracranial occlusion, in
whom the procedure can be started within 6 hours from onset, has been proven
safe and effective. Still, a considerable proportion of patients do not recover
despite recanalization. This is for a major part attributable to incomplete
microvascular reperfusion (IMR). Antiplatelet agents and heparin may reduce
IMR. Yet, it is unknown whether periprocedural antiplatelet agents and
anticoagulant medication in patients with acute ischemic stroke treated with
IAT can improve clinical outcome.
Study objective
To assess the effect of acetylsalicylic acid (ASA) and unfractionated heparin,
alone, or in combination, in patients with AIS, who undergo IAT for a confirmed
intracranial anterior circulation occlusion.
Study design
This is a multicenter phase III randomized clinical trial with open-label
treatment using a 2x2 factorial design, comparing IV ASA and one dose of
unfractionated heparin as co-medication in IAT. It has blind assessment of
primary outcomes and of neuro-imaging at baseline and follow-up.
Intervention
Treatment with unfractionated heparin in a low dose (loading dose of 5000 IU
followed by 500 IU/hour x 6 hours). Treatment with IV acetylsalicylic acid (300
mg). At 24 hours after start of IAT, all patients will receive antiplatelet
therapy or anticoagulation according to local protocol, at the discretion of
the treating physician.
Study burden and risks
Clinical equipoise and considerable practice variation exist with respect to
the periprocedural antiplatelet and anticoagulant treatment. There is a
potential benefit, and a low risk which includes the risk of intracranial
hemorrhage. However, every hour delay in reperfusion leads to 6-7% absolute
risk reduction in good outcome. We therefore make use of deferred written
informed consent (by proxy).
Wytemaweg 80
Rotterdam 3015CN
NL
Wytemaweg 80
Rotterdam 3015CN
NL
Listed location countries
Age
Inclusion criteria
a clinical diagnosis of acute ischemic stroke; caused by proximal intracranial
anterior circulation occlusion (distal intracranial carotid artery or middle
(M1/proximal M2) or anterior (A1/A2) cerebral artery confirmed by neuro-imaging
(CTA or MRA); CT or MRI ruling out intracranial hemorrhage; treatment possible
(groin puncture) within 6 hours from symptom onset or last seen well; a score
of at least 2 on the NIH Stroke Scale; age of 18 years or older; written
informed consent (deferred).
Exclusion criteria
- Pre-stroke disability which interferes with the assessment of functional
outcome at 90 days, i.e. mRS >2;
- Treatment with IV alteplase, despite the following contra-indications for IV
alteplase: cerebral infarction in the previous 6 weeks with residual
neurological deficit or signs of recent infarction on neuroimaging, previous
intracerebral hemorrhage in the previous 3 months, INR exceeding 1.7, prior use
of direct oral anticoagulant (DOAC)
- IV alteplase infusion >4.5 hours after symptom onset;
- Contra-indications for ASA/unfractionated heparin, for instance: allergy,
recent hemorrhage, heparin induced thrombocytopenia;
- INR exceeding 3.0
- Known hemorrhagic diathesis or known thrombopenia (<90^9/L)
- Therapeutic heparin use
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 |
|---|---|
| EudraCT | EUCTR2017-001466-21-NL |
| ISRCTN | ISRCTN76741621 |
| CCMO | NL61364.078.17 |