LATE-MT: Large Artery Occlusion Treated in Extended Time With Mechanical Thrombectomy Trial

Sponsor

The George Institute for Global Health, China (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05326932

Collaborator

Changhai Hospital (Other)

382

Enrollment

Arms

30.1

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Acute Ischemic Stroke	Procedure: Mechanical thrombectomy	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

382 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jul 30, 2022

Anticipated Primary Completion Date :

Oct 30, 2024

Anticipated Study Completion Date :

Jan 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention group Mechanical thrombectomy to be initiated as soon as possible after randomisation.	Procedure: Mechanical thrombectomy 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.
No Intervention: Control group Patients assigned to the control group will avoid treating MT and only receive the standard medical treatment according to local guidelines.

Arm

Intervention/Treatment

Experimental: Intervention group

Mechanical thrombectomy to be initiated as soon as possible after randomisation.

Procedure: Mechanical thrombectomy

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.

No Intervention: Control group

Patients assigned to the control group will avoid treating MT and only receive the standard medical treatment according to local guidelines.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Neurological impairment [24 hours and 7 days]
Measured by scores on the National Institute of Health Stroke Scale (NIHSS). The value range 0-42: higher scores mean a worse outcome.
Death or major disability [90 days]
modified Rankin scale (mRS) 3-6
Separately on death and disability [90 days]
modified Rankin scale (mRS) 3-5
Health-related Quality of Life (HRQoL) [90 days]
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.
Utility-weighted modified Rankin scale scores [90 days]
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.
Duration of hospitalization [90 days]
Days of hospitalization
Residence [90 days]
Days of residence
Hospital service costs [90 days]
Health economic measurement
Infarct volume on DWI, or CT [24 hours]
Infarct volume on DWI, or CT if DWI not feasible
Recanalization [24 hours after MT]
Recanalization confirmed on imaging

Other Outcome Measures

Intracerebral hemorrhage (ICH) [24 hours and 90 days]
a) symptomatic ICH, based on previous criteria; b) ICH of any type in brain imaging
Death [7 days and 90 days]
Death
Serious adverse events (SAE) [90 days]
All SAE during follow-up in all randomized patients

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)