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

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; 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.

Inclusion Criteria:

1. Age ≥18 years
2. Present 24-72 hours of stroke onset or last seen well
3. 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
4. National Institute of Health stroke scale (NIHSS) ≥6 at randomisation
5. Viable cerebral tissue on computerized tomography perfusion (CTP) assessed: infarct core volume <50 mL, mismatch ratio ≥1.8, and mismatch volume ≥15 mL
6. Written informed consent (by patient or proxy, according to local requirements)

Exclusion Criteria:

Clinical Exclusion Criteria

1. 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
2. Major co-morbid disease that could interfere with outcome assessments and follow-up (e.g. cancer, severe heart failure, kidney failure)
3. Pregnancy
4. Unable to undergo a CTP
5. Known allergy to iodine, heparin, anaesthesia, or other definite contraindication to receiving endovascular treatment (EVT) procedure
6. Seizures at stroke onset or before randomization and baseline NIHSS scores cannot be accurately determined
7. Baseline blood glucose of <50 mg/dL (2.78 mmol/L) or >400 mg/dL (22.20 mmol/L)
8. Baseline platelet count < 50,000/uL
9. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with International normalized ratio (INR) >3
10. Severe, sustained hypertension that can not be controlled by medication (systolic BP >220 mmHg or diastolic BP >120 mmHg)
11. Presumed septic embolus, suspicion of bacterial endocarditis
12. EVT attempted after stroke onset
13. Unlikely to participate in follow-up assessments
14. Currently participating in another trial that may affect outcomes.
15. 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

1. Intracranial hemorrhage (ICH), including parenchymal hemorrhage, ventricular hemorrhage, subarachnoid hemorrhage, and subdural/exsanguination
2. Evidence of intracranial malignant tumor
3. Significant mass effect with midline shift
4. Aortic dissection
5. Intracranial stent implanted in the same vascular territory
6. 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
7. 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)

Data can be shared with bona fide researchers after the publication of the main results, based on a submitted protocol to the steering committee of LATE-MT.

Data sharing will be available from 12 months after the publication of the main results.

1. The data sharing will be only for the purposes of health and medical research and within the constraints of the consent under which the data were originally gathered.
2. The Custodian of the Collection will not consider any Proposals for data sharing that unblind, or potentially unblind, randomised comparisons in active / ongoing trials.
3. Requesters should be employees of a recognised academic institution, health service organisation, commercial research organisation or from the pharmaceutical industry. Requesters must have experience in medical research.
4. Requesters must be able to demonstrate through their peer review publications in the area of interest their ability to carry out the proposed use of the requested dataset from a Collection.
5. The Requesters must not have a conflict of interest that may potentially influence their interpretation of any analyses.