Large Stroke Therapy Evaluation
Large Stroke Therapy Evaluation
Stroke represents the fourth leading cause of death in industrialized nations, after heart
 disease, cancer, and chronic lower respiratory disease. The overall burden of stroke will
 rise dramatically in the next 20 years due to an ageing population. Approximately one-quarter
 of the patients suffering a stroke die within one year after the initial event and stroke is
 a leading cause of serious long-term disability. Although mechanical thrombectomy (MT) has
 become the standard of care for acute ischemic stroke with proximal large vessel occlusion
 (LVO) in the anterior circulation, the management of patients harboring proximal occlusion
 but presenting minor-to-mild stroke symptoms, has not yet been determined by these recent
 randomized clinical trials. However, patients with proximal occlusions may present with a low
 National Institutes of Health Stroke Scale (NIHSS) 10, a proximal intraarterial occlusion
 being present in up to 28% when considering patients with an NIHSS ≤ 411. In observational
 study, patient with minor or mild stroke symptoms and LVO have a high risk of both clinical
 worsening and bad outcome. The STAIR (Stroke Treatment Academic Industry Roundtable) meeting
 aims to advance acute stroke therapy development through collaboration between academia,
 industry, and regulatory institutions13. In pursuit of this goal and building on the
 available level I evidence of benefit from endovascular therapy (EVT) in large vessel
 occlusion stroke, STAIR IX consensus recommendations were developed that outline priorities
 for future research in EVT.
The LASTE hypothesis is that patient harbouring a large ischemic core stroke at presentation,
 may still benefit from mechanical thrombectomy, given the very poor natural history of
 patient managed by a standalone medical therapy.

 The threshold of ASPECTS 5 to set a benefit for treatment was inspired by initial large
 medical trials using IV t-PA25-27 (Samurai-CT ALBERTA Score IV cohort). In the paradigm of
 acute and complete reperfusion, radiographic infarct stroke volume may be partially
 reversible and thus the resulting final infarct may be smaller compared to the one in
 non-re-perfused patients who will consequently have poorer clinical outcomes. By now, large
 core patients defined as ASPECTS 0-5 were excluded from most randomized clinical trials
 resulting in a lack of unequivocal evidence of benefit in this patient population.

 Analyses of several prospective cohorts suggest signals of benefit in favor of thrombectomy
 in patients with large baseline core. In the prospective cohort ETIS, LAPERGUE et al reported
 a rate of good outcome of 34% in the subgroup of patient with ASPECT 4-5. In the prospective
 cohort analysis RECOST, a mean mRS score of 34% in a group of patient presenting ASPECT 0-5
 treated with mechanical thrombectomy, versus 9% of good outcome in the medical group,
 suggesting a benefit to treat LVO harbouring a large core. The strongest argument in favor of
 benefit of EVT even in patients with large core is provided by the six completed randomized
 endovascular stroke trials. These trials did prove that Combined Approach Mechanical + IV
 t-PA, is superior to standalone IV lytics, mRs score ≤ 2 ranging from 33% and up to 72%, but
 Large Core Infarction were largely excluded. Nonetheless a pooled analysis of these trials
 revealed that a minority of patients with large baseline core were still randomized. In MR
 CLEAN study, despite no exclusion criteria defined in the initial protocol, the median ASPECT
 score of the cohort was 9 out of 10. In SWIFT-PRIME study, the mean ASPECT score of the
 cohort was 7, and in REVASCAT study it was 6.8.

 The LASTE protocol "Large Stroke Therapy Evaluation" aims to study the efficacy and safety of
 mechanical thrombectomy in the acute phase of cerebral infarction less than 7 hours for
 patients with a large volume of necrosis defined by a score ASPECT from 0 to 5. The patients
 will be followed 6 months after the stroke.
Inclusion Criteria:

 1. Subject is ≥ 18 years old at inclusion (no upper age limit)

 2. Clinical signs consistent with acute ischemic stroke with symptoms onset or time last
 known well (TLKW) ≤ 6.5 h from randomization (With the goal of remaining within 7
 hours from TLKW till treatment), or with negative FLAIR on MRI, if TLKW is unknown

 3. Proven Large Ischemic Core defined as: ASPECT Score 0 to 5 on non-contrast CT or
 Diffusion Weighted Imaging (DWI)-MRI. In patients ≥ 80 years : ASPECT score 4 or 5.

 (ASPECTS on MRI will be calculated in the following way: an ASPECTS region will
 considered to be affected if > 30% of its area demonstrates restricted diffusion)

 4. Proved anterior circulation intracranial large vessel occlusion on CTA or MRA
 (intracranial ICA, M1, M1-M2)

 5. Patient or patient's representative has received information about the study and has
 signed and dated the appropriate Informed Consent Form, or fulfilling the criteria for
 emergent consent

 6. Selection imaging performed maximum 3 hours from randomization

 7. Anticipated possibility to start the procedure (arterial access) within 30 minutes
 after randomization

 8. Pre stroke mRS ≤ 1

 9. Subjects receiving antiaggregant and/or anticoagulant agents (at any mode of
 administration) within the last 24 hours from screening are eligible for participation

 General Exclusion Criteria:

 1. Anticipated impossibility to start the procedure (arterial access) within 30 minutes
 after randomization.

 2. Known absence of vascular access.

 3. Known contrast or endovascular product life-threatening allergy.

 4. Female who is known to be pregnant or lactating at time of admission

 5. Patient presents severe or fatal co-morbidities or life expectancy under 6 months that
 will likely interfere with the improvement or follow-up or that will render the
 procedure unlikely to benefit the patient.

 6. Patient unable to present or be available for follow-up.

 7. Pre-existing neurological or psychiatric disease that would confound the neurological
 or functional evaluations.

 8. Evidence of vessel recanalization prior to randomization.

 9. Seizures at stroke onset if it makes the diagnosis of stroke doubtful and precludes
 obtaining an accurate baseline NIHSS assessment.

 10. Current participation in another investigational drug study.

 11. Suspicion of aortic dissection based on medical history, clinical evaluation or/and
 imaging.

 12. Major patients under guardianship.

 Imaging Exclusion Criteria:

 1. Evidence of intracranial haemorrhage on CT/MRI

 2. Excessive tortuosity of cervical vessels on CTA/MRA that would likely result in
 unstable access platform

 3. High Suspicion of underlying intracranial stenosis on CTA/MRA/digital subtraction
 angiography (DSA)

 4. Suspected cerebral vascular disease (e.g. vasculitis) based on medical history and
 CTA/MRA/DSA

 5. Presumed calcified Embolus or Intracranial Stenosis decompensation

 6. Intracranial stent implanted in the same vascular territory that would preclude the
 safe deployment/removal of the stentriever device

 7. Occlusions in multiple vascular territories (e.g.: bilateral anterior circulation, or
 anterior circulation/vertebrobasilar system) confirmed on CTA/MRA/DSA.

 8. Significant mass effect with midline shift as confirmed on CT/MRI

 9. Any cervical ICA lesion (Tandem), that requires stent placement

 10. Isolated proximal cervical ICA occlusions