Large Artery Occlusion Treated in Extended Time With Mechanical Thrombectomy Trial

Study Overview
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Brief Summary
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A multi-center, prospective, randomized, open-label, adaptive group sequential designed, blinded endpoint assessment (PROBE) clinical trial of endovascular treatment among selected AIS

Detailed Description
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The LATE-MT trial aims to determine that compared with standard medical care without MT, performing MT in a time window that exceeds 24 hours after last seen well, is superior on the functional outcome in AIS patients due to LVO who have been carefully selected by clinical and imaging criteria. The secondary aims include comparing with standard medical care without MT, to determine whether performing MT exceeding 24 hours of last known well is safe on the risks of any ICH, sICH, and any SAE. Other secondary aims include early improvement in neurological recovery as measured by NIHSS scores at 7 days; successful recanalization rate; imaging measurements of infarct size at 24-48 hours; death or major disability (mRS 3-6); separately on death and disability (mRS 3-5); HRQoL using Euro-QoL EQ-5D questionnaire; utility-weighted modified Rankin scale scores; duration of hospitalization; residence; and hospital service costs.

Official Title
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An Investigator Initiated and Conducted, Prospective, Multicenter, Randomized Outcome-blinded Study of Treating Mechanical Thrombectomy Exceeding 24 Hours in Patients With Acute Ischemic Stroke Due to Large Vessel Occlusion

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Procedure: Mechanical thrombectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Present 24-72 hours of stroke onset or last seen well Clinical diagnosis of AIS due to anterior circulation LVO (from internal carotid artery (ICA) extracranial segment to middle cerebral artery (MCA) M1 and M2 segment) on brain imaging National Institute of Health stroke scale (NIHSS) ≥6 at randomisation Viable cerebral tissue on computerized tomography perfusion (CTP) or magnetic resonance imaging perfusion (MRP) assessed: infarct core volume <50mL, mismatch ratio ≥1.8 and mismatch volume ≥15mL Written informed consent (by patient or proxy, according to local requirements) Exclusion Criteria: Clinical Exclusion Criteria Considered unlikely to benefit from trial (e.g. advanced dementia, major pre-stroke disability (prior modified Rankins scale (mRS) ≥2), high likelihood of early death), as judged by the responsible treating clinician Major co-morbid disease that could interfere with outcome assessments and follow-up (e.g. cancer, severe heart failure, kidney failure) Pregnancy Unable to undergo a CTP or MRP Known allergy to iodine, heparin, anaesthesia, or other definite contraindication to receiving endovascular treatment (EVT) procedure Seizures at stroke onset or before randomization and baseline NIHSS scores cannot be accurately determined Baseline blood glucose of <50mg/dL (2.78 mmol/L) or >400mg/dL (22.20 mmol/L) Baseline platelet count <50,000/uL Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with International normalized ratio (INR) >3 Severe, sustained hypertension (systolic blood pressure (BP) >220 mmHg or diastolic BP >120 mmHg) Presumed septic embolus, suspicion of bacterial endocarditis EVT attempted after stroke onset Unlikely to participate in follow-up assessments Currently participating in another trial that may affect outcomes. Any other condition that, in the opinion of the investigator will pose a significant hazard to the subject if participating in the trial. Neuroimaging Exclusion Criteria Intracranial hemorrhage (ICH), including parenchymal hemorrhage, ventricular hemorrhage, subarachnoid hemorrhage, and subdural/exsanguination Evidence of intracranial tumor (except small meningioma) Significant mass effect with midline shift Aortic dissection Intracranial stent implanted in the same vascular territory Any other condition that may affect EVT procedure, like the tortuous vascular path the device is difficult to reach the target position or difficult to recover Occlusions in multiple vascular territories confirmed on Computerized tomography angiography (CTA)/ Magnetic resonance imaging angiography (MRA) (e.g. bilateral MCA occlusions, or an MCA and a basilar artery occlusion)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>Mechanical thrombectomy to be initiated as soon as possible after randomisation. | Procedure: Mechanical thrombectomy<br>* Subjects in intervention group will receive MT as soon as possible. Investigators and clinicians should strive to reduce delays of pre-surgery procedure and follow the local standard guideline of MT during the operation and perioperative period. All CFDA approved devices are allowed in this trial. Angioplasty and stent placement can be performed at the discretion of the physicians. Base on site experience, the randomization-operation start period should be within 60 minutes.<br>|
| No Intervention: Control group<br>Patients assigned to the control group will avoid treating MT and only receive the standard medical treatment according to local guidelines. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional recovery (level of disability) | Shift (improvement) in scores on the modified Rankin scale (mRS). The value range 0-6: higher scores mean a worse outcome. | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurological impairment | Measured by scores on the National Institute of Health Stroke Scale (NIHSS). The value range 0-42: higher scores mean a worse outcome. | 24 hours and 7 days | 
| Death or major disability | modified Rankin scale (mRS) 3-6 | 90 days | 
| Separately on death and disability | modified Rankin scale (mRS) 3-5 | 90 days | 
| Health-related Quality of Life (HRQoL) | using EQ-5D. European Quality of Life 5-dimensional questionnaire. The EQ-5D comprises five dimensions of health: mobility, ability to self-care, ability to undertake usual activities, pain and discomfort, and anxiety and depression. . EQ-5D-5L, includes five levels of severity for each dimension (no problems, slight problems, moderate problems, severe problems, and extreme problems). The value range 0-100: Higher scores mean a worse outcome. | 90 days | 
| Utility-weighted modified Rankin scale scores | Utility-weighted modified Rankin scale scores. The value range from 0 to 10: higher scores mean a better outcome. Higher scores mean a worse outcome. | 90 days | 
| Duration of hospitalization | Days of hospitalization | 90 days | 
| Residence | Days of residence | 90 days | 
| Hospital service costs | Health economic measurement | 90 days | 
| Infarct volume on DWI, or CT | Infarct volume on DWI, or CT if DWI not feasible | 24 hours | 
| Recanalization | Recanalization confirmed on imaging | 24 hours after MT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute ischemic stroke, Large vessel occlusion, Mechanical thrombectomy, Extended time, Randomised clinical trial