Clinical trial NCT03811769: Large Stroke Therapy Evaluation
Official title: Evaluation of Acute Mechanical Revascularisation in Large Stroke (ASPECTS 0-5) With Large Vessel Occlusion Within 7 Hours After Stroke Onset or Last Known Well
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Stroke
Keywords: Mechanical thrombectomy
Stroke
Proximal intracranial arterial occlusions
Large vessel occlusion
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
First posted: 2019-01-22
Enrollment: 335
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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. Acute ischemic stroke (AIS) due to large vessel occlusion (LVO) is a potentially devastating event, with a poor prognosis in the absence of timely revascularization. Whether in patients with large anterior circulation stroke, direct mechanical intervention is equally effective, superior or inferior to bridging thrombolysis remains a matter of debate.

Thus, this procedure, is now the recommended standard of care for selective patients with LVO in the anterior circulation. When performed with newer generation devices (mainly stent retrievers), more stringent imaging selection criteria and more efficient workflow than in previous trials, significantly reduces disability rates after AIS caused by LVO in the anterior circulation.

The STAIR (Stroke Treatment Academic Industry Roundtable) meeting aims to advance acute stroke therapy development through collaboration between academia, industry, and regulatory institutions. 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.

Detailed description: 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.

Eligibility criteria: 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 TLKW ≤ 6.5 hours from randomization, or with negative FLAIR on MRI if TLSW is unknown, with treatment started within 7 hours.
3. Proven Large Ischemic Core defined as: ASPECT Score ≤ 5 on non-contrast CT or DWI-MRI, and in patients ≥ 80 years: ASPECT = 3 to 5 on non-contrast CT or DWI-MRI
4. Proved anterior circulation intracranial large vessel occlusion on CTA or MRA (intracranial ICA, M1, M1-M2). The MCA - M1 segment is defined as the first branch of the intracranial ICA which courses horizontally from its branching point off the ICA through the Sylvian fissure up to the first bifurcation distal to the lenticulo-striate arteries, in the Sylvian fissure. M2 is defined as the portions of the MCA distal to the first bifurcation or trifurcation, but prior to the second bifurcation.
5. Patient or patient's representative has received information about the study and has signed and dated the appropriate Informed Consent Form
6. Selection imaging performed ≤ 3 hours before 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.
10. NIHSS \> 6
11. For patients for whom thrombolytic therapy, such as IV t-PA, is indicated, such treatment is initiated as soon as possible and within the accepted clinical guidelines as measured from stroke symptom onset.

Exclusion criteria:

1. Known absence of vascular access.
2. Known contrast or endovascular product life-threatening allergy.
3. Female who is known to be pregnant or lactating at time of admission
4. 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.
5. Patient unable to present or be available for follow-up.
6. Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations.
7. Evidence of vessel recanalization prior to randomization.
8. Seizures at stroke onset if it makes the diagnosis of stroke doubtful and precludes obtaining an accurate baseline NIHSS assessment.
9. Current participation in another investigational drug study.
10. Suspicion of aortic dissection based on medical history, clinical evaluation or/and imaging.
11. Major patients under guardianship.
12. Blood glucose \< 50 mg/dL or \> 400 mg/dL
13. Cr \> 4.0 mg/dL, unless the patient is on dialysis
14. Platelet count \< 50000/uL
15. INR \> 3.0 or PTT \> 3 times upper limit of normal (ULN)

Imaging Exclusion Criteria:

1. Isolated proximal cervical ICA occlusions or proximal cervical ICA occlusions with MCA-M1 or intracranial ICA occlusion requiring stent placement, and isolated M2 occlusions on the pre-randomization neuro-imaging
2. Evidence of intracranial hemorrhage on CT/MRI
3. Excessive tortuosity of cervical vessels on CTA/MRA that would likely result in unstable access platform
4. High Suspicion of underlying intracranial stenosis on CTA/MRA/DSA
5. Suspected cerebral vascular disease (e.g. vasculitis) based on medical history and CTA/MRA/DSA
6. Presumed calcified Embolus or Intracranial Stenosis decompensation
7. Intracranial stent implanted in the same vascular territory that would preclude the safe deployment/removal of the stentriever device
8. Occlusions in multiple vascular territories (e.g.: bilateral anterior circulation, or anterior circulation/vertebrobasilar system) confirmed on CTA/MRA/DSA.
9. Significant mass effect with midline shift as confirmed on CT/MRI
10. Any ipsilateral cervical ICA lesion (Tandem), that requires stent placement

Primary outcomes:
measure: Evaluation of patient's condition
timeFrame: 3 months
Secondary outcomes:
measure: Evaluation of patient's condition
timeFrame: 6 months
measure: Evaluation of good functional outcome
timeFrame: 3 and 6 months
measure: Evaluation of functional outcome
timeFrame: 3 and 6 months
measure: Evaluation of treatment effect
timeFrame: 3 and 6 months
measure: Evaluation of quality of life
timeFrame: 3 and 6 months
measure: Evaluation of decompressive condition
timeFrame: 7 days
measure: Evaluation of medical response
timeFrame: Day 5-7 or discharge, whichever is earlier
measure: Evaluation of medical condition
timeFrame: 1 day
Other outcomes:
Locations:
city: Montpellier
country: France
facility: Hopital Gui De Chauliac
Study officials:
affiliation: Hôpital Gui de Chauliac
name: Vincent COSTALAT, PU-PH
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Gui de Chauliac
name: Caroline ARQUIZAN, PH
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Foch
name: Bertrand LAPERGUE
role: PRINCIPAL_INVESTIGATOR
affiliation: Cooper Neurological Institute
name: Tudor JOVIN, PU-PH
role: PRINCIPAL_INVESTIGATOR
References: