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Large Stroke Therapy Evaluation

Not Applicable
Terminated
Conditions
Stroke
Interventions
Procedure: Mechanical Thrombectomy
Other: Best Medical Therapy
Registration Number
NCT03811769
Lead Sponsor
University Hospital, Montpellier
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
335
Inclusion Criteria

Not provided

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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Mechanical Thrombectomy (MT)Mechanical ThrombectomyEndovascular treatment (thrombectomy) associated with the best medical treatment
Best Medical Therapy (BMT)Best Medical TherapyBest treatment medical probably associated to the rescue endovascular treatment in case of neurological deterioration
Primary Outcome Measures
NameTimeMethod
Evaluation of patient's condition3 months

Shift on the mRS at 90 days in experimental group vs the control group

Secondary Outcome Measures
NameTimeMethod
Evaluation of patient's condition6 months

The degree of disability at 180 days (shift on the mRS combining scores of 5 and 6)

Evaluation of functional outcome3 and 6 months

Rate of patients with a favorable outcome at 90 and 180 days, defined as mRS 0-3

Evaluation of quality of life3 and 6 months

Quality of life at 90 and 180 days assessed by EuroQol/EQ-5D

Evaluation of treatment effect3 and 6 months

Distribution of utility weighted mRS (UW mRS) at 90 and 180 days

Evaluation of medical condition1 day

Change in infarct volumes on CT or MRI from baseline to 24 hours post randomization

Evaluation of good functional outcome3 and 6 months

Rate of patients with a good functional outcome at 90 days and 180 days, defined as mRS 0-2

Evaluation of medical responseDay 5-7 or discharge, whichever is earlier

Rate of patients with "early good response" at Day 5-7/Discharge (whichever is earlier), defined as a NIHSS drop of ≥ 8 points from baseline or NIHSS score 0 or 1

Evaluation of decompressive condition7 days

Rate of patients with secondary decompressive craniectomy within 7 days

Trial Locations

Locations (1)

Hopital Gui De Chauliac

🇫🇷

Montpellier, France

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