Evaluation of Endovascular Treatment in Acute Intracranial Distal Medium Vessel Occlusion Stroke

Sponsor

The First Affiliated Hospital of University of Science and Technology of China (Other)

Overall Status

Recruiting

CT.gov ID

NCT06146790

Collaborator

(none)

564

Enrollment

Location

Arms

Anticipated Duration (Months)

20.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Rationale: Distal Medium Vessel Occlusion (MeVO) are thought to cause as many as 25% to 40% of all acute ischemic strokes (AIS). Despite their relatively high frequency, there is no consensus regarding the optimal management of these patients. However, the fact that AIS related to MeVO often results in significant disability despite best medical treatment (including intravenous thrombolysis, IVT) calls for novel treatment approaches. Fortunately, a growing number of non-randomized studies have now been published demonstrating the feasibility of endovascular treatment (EVT) for MeVO strokes. These studies have demonstrated that distal EVT leads to high rates of successful reperfusion and may be performed with a comparable safety profile to that of EVT for proximal arterial occlusions. Therefore, a strong rational exists to test the safety and efficacy of EVT for MeVO stokes in a prospective randomized clinical trial.

Objectives: The primary objective of this study is to evaluate the hypothesis that endovascular thrombectomy is superior to standard medical management in achieving more favorable outcomes according to the modified Rankin Scale scores at 90 days in subjects presenting with acute ischemic stroke related to a distal medium vessel occlusion within 12 hours from symptom onset (defined as time last know well, TLKW).

Secondary objectives include the assessment of the cost-effectiveness of endovascular thrombectomy in the medium vessel occlusion (MeVO) population as well as its impact on health-related quality of life.

Study design: The study is a prospective, multicenter, investigational, randomized, controlled, open-label study with blinded endpoint evaluation (PROBE design) and an adaptive design with population enrichment.

Study population: Subjects presenting with acute ischemic stroke within 12 hours from TLKW and whose strokes are attributable to a distal medium vascular occlusion defined as M2 segment or M3 segment of the MCA, the ACA (A1, A2, or A3 segments), or the PCA (P1, P2 or P3 segments) with evidence of salvageable brain tissue on perfusion imaging, M2 segment vessel diameter should not exceed 2.5 mm.

Primary outcome: Shift in distribution of all levels of the 90-day the modified Rankin Scale with levels 5-6 combined (mRS; 0, 1, 2, 3, 4, 5-6) as assessed by structured assessment.

Condition or Disease	Intervention/Treatment	Phase
Acute Ischemic Stroke Endovascular Thrombectomy	Procedure: endovascular treatment Other: Standard medical management	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

564 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Evaluation of Endovascular Treatment in Acute Intracranial Distal Medium Vessel Occlusion Stroke - a Multicenter, Randomized Controlled, Clinical Trial

Anticipated Study Start Date :

Dec 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2025

Anticipated Study Completion Date :

Mar 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Endovascular treatment+ standard medical management For the subjects randomized to endovascular treatment (EVT), treatment initiation is defined as the date and time of arterial puncture. Ideally, femoral artery puncture will occur within 30 minutes of randomization and no longer than 60 minutes after the completion of the qualifying imaging. Treatment initiation (arterial puncture) must occur before 12 hours since the subject was last known well. Date and time of arterial puncture, revascularization, and procedure end will be recorded. It is expected that the interventional procedure will be completed within two (2) hours of arterial access. If an appropriate thrombus or residual stenosis is identified, the choice of EVT strategy will be made by the treating neurointerventionalist. All mechanical thrombectomy devices for EVT, which are approved by CFDA for this purpose, are allowed in the trial.	Procedure: endovascular treatment For the subjects randomized to endovascular treatment (EVT) treatment initiation is defined as the date and time of arterial puncture. Ideally, femoral artery puncture will occur within 30 minutes of randomization and no longer than 60 minutes after the completion of the qualifying imaging. Treatment initiation (arterial puncture) must occur before 12 hours since the subject was last known well.Date and time of arterial puncture, revascularization, and procedure end will be recorded. It is expected that the interventional procedure will be completed within two (2) hours of arterial access. If an appropriate thrombus or residual stenosis is identified, the choice of EVT strategy will be made by the treating neurointerventionalist. All mechanical thrombectomy devices for EVT, which are approved by CFDA for this purpose, are allowed in the trial.
Active Comparator: Standard medical management Standard medical management	Other: Standard medical management Standard medical management

Arm

Intervention/Treatment

Experimental: Endovascular treatment+ standard medical management

For the subjects randomized to endovascular treatment (EVT), treatment initiation is defined as the date and time of arterial puncture. Ideally, femoral artery puncture will occur within 30 minutes of randomization and no longer than 60 minutes after the completion of the qualifying imaging. Treatment initiation (arterial puncture) must occur before 12 hours since the subject was last known well. Date and time of arterial puncture, revascularization, and procedure end will be recorded. It is expected that the interventional procedure will be completed within two (2) hours of arterial access. If an appropriate thrombus or residual stenosis is identified, the choice of EVT strategy will be made by the treating neurointerventionalist. All mechanical thrombectomy devices for EVT, which are approved by CFDA for this purpose, are allowed in the trial.

Procedure: endovascular treatment

For the subjects randomized to endovascular treatment (EVT) treatment initiation is defined as the date and time of arterial puncture. Ideally, femoral artery puncture will occur within 30 minutes of randomization and no longer than 60 minutes after the completion of the qualifying imaging. Treatment initiation (arterial puncture) must occur before 12 hours since the subject was last known well.Date and time of arterial puncture, revascularization, and procedure end will be recorded. It is expected that the interventional procedure will be completed within two (2) hours of arterial access. If an appropriate thrombus or residual stenosis is identified, the choice of EVT strategy will be made by the treating neurointerventionalist. All mechanical thrombectomy devices for EVT, which are approved by CFDA for this purpose, are allowed in the trial.

Active Comparator: Standard medical management

Standard medical management

Other: Standard medical management

Standard medical management

Outcome Measures

Primary Outcome Measures

The 90-day modified Rankin Scale (mRS) [90 (± 14 days) after procedure]
Shift in distribution of all levels of the 90-day modified Rankin Scale with levels 5-6 combined (mRS; 0, 1, 2, 3, 4, 5-6) as assessed by structured assessment.

Secondary Outcome Measures

Modified Rankin Scale (mRS) [90 (± 14 days) after procedure]
Shift in distribution of the 90-day mRS (0;1;2;3;4;5;6) as assessed by structured assessment.
Independent Outcome [90 (± 14 days) after procedure]
Rates of Independent Outcome defined as mRS ≤2 and/ or equal to Baseline mRS at 90 days
Excellent Outcome [90 (± 14 days) after procedure]
Rates of Excellent Outcome defined as mRS ≤1 and/ or equal to Baseline mRS at 90 days
Good Functional Outcomes [90 (± 14 days) after procedure]
Rates of Good Functional Outcomes adjusted for the baseline mRS and stroke severity (NIHSS) according to the modified Rankin Scale scores at 90 days as following: If NIHSS <10 and Baseline mRS 0 or 1: 90-day mRS ≤1 If NIHSS <10 and Baseline mRS 2: 90-day mRS ≤2 If NIHSS ≥10 and Baseline mRS 0 or 1: 90-day mRS ≤2 If NIHSS ≥10 and Baseline mRS 2: 90-day mRS ≤3
Successful reperfusion on final angiography of thrombectomy [Within 5 minutes at final angiography of thrombectomy]
EVT arm only: Final reperfusion grades according to the extended Thrombolysis in Cerebral Infarction (eTICI) scale and the rates of First Pass Effect (eTICI ≥2c) and Modified First Pass Effect (eTICI ≥2b50)
Utility-weighted modified Rankin scale [90 (± 14 days) after procedure]
Mean score for disability on the utility-weighted modified Rankin scale (UW-mRS) at 90 days
Final infarct volume (FIV) and infarct growth at 24 hours (-2/+12 hours) [24 hours (-2/+12 hours) after procedure]
Final infarct volume (FIV) and infarct growth (FIV - baseline infarct on CTP or DWI) evaluated on CT or MRI at 24 hours (-2/+12 hours)
Final infarct volume (FIV) and infarct growth at 3-5 days after procedure [3-5 days after procedure]
Final infarct volume (FIV) and infarct growth (FIV - baseline infarct on CTP or DWI) evaluated on CT or MRI at 3-5 days (if available)
Clinical improvement at 24 hours [24 hours after procedure]
Clinical improvement at 24 hours calculated as the difference between 24-hour and baseline NIHSS score
Brain tissue reperfusion evaluated by CT or MRI perfusion at 24 hours in both treatment groups (if available) [24 hours after procedure]
Evaluate brain tissue reperfusion after treatment
Vessel patency evaluated by CTA or MRA perfusion at 24 hours in both treatment groups (if available) [24 hours after procedure]
Evaluate vascular patency after treatment
Score on the EuroQoL 5-dimensions 5-level (EQ5D-5L) at 90 days (±14 days) [90 (± 14 days) after procedure]
The EQ-5D-5L is a questionnaire designed to assess five dimensions of life quality related to mobility, self-care, usual activities, pain or discomfort, and anxiety or depression (range: 0.39 to 1, with a higher score indicating a higher quality of living)
level of activities of daily living (Barthel index, BI) at 90 days (±14 days) [90 (± 14 days) after procedure]
Level of activities of daily living

Other Outcome Measures

All-cause mortality [90 (± 14 days) after procedure]
All-cause mortality within 90 days
Mortality due to index stroke [90 (± 14 days) after procedure]
Mortality within 90 days due to index stroke
Symptomatic intracranial hemorrhage (SICH) defined as per the modified SITS-MOST definition [24 hours (-2/+12H) after procedure]
local or remote parenchymal hemorrhage type 2, subarachnoid hemorrhage, and/or intraventricular hemorrhage on the post-treatment imaging scan, combined with a neurological deterioration of 4 points or more on the NIHSS from baseline, or from the lowest NIHSS value between baseline and 24 h (-2/+12), or leading to death that the CEC/DSMB judges is causative of the deterioration.
Symptomatic intracranial hemorrhage (SICH) defined as per the Heidelberg Classification [24 hours (-2/+12H) after procedure]
≥4 points total NIHSS at the time of diagnosis compared to immediately before worsening. Note that a 4 points change is not compared with the baseline admission NIHSS score but instead to the immediate predeterioration neurological status ≥2 point in one NIHSS category. The rationale for this is to capture new hemorrhages that produce new neurological symptoms, making them clearly symptomatic but not causing worsening in the original stroke territory. For example, a new remote hemorrhage in the contralateral occipital lobe may cause new hemianopia that is clearly symptomatic, but the patient will not have worsening of ≥4 points on the NIHSS score Leading to intubation/hemicraniectomy/EVD placement or other major medical/surgical intervention. Absence of alternative explanation for deterioration.
Rate of intracranial hemorrhage [24 hours (-2/+12H) after procedure]
The incidence of any intracranial hemorrhage measured at 24 (-2/+12) hours as graded by the central core-lab using the Heidelberg classification criteria.
Rate of procedure-related vessel perforation [during mechanical thrombectomy (MT) procedure]
Vessel perforation related to mechanical thrombectomy
Rate of Procedure-related vessel dissection [during mechanical thrombectomy (MT) procedure]
Vessel dissection related to mechanical thrombectomy
Rate of Procedure-related new embolization [during mechanical thrombectomy (MT) procedure]
Embolization to a new territory during mechanical thrombectomy (MT) procedure
Rate of significant extracranial hemorrhage [during mechanical thrombectomy (MT) procedure]
Significant extracranial hemorrhage (e.g., access site, retroperitoneal hematoma) requiring blood transfusion and/ or surgical intervention.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥18 years (no upper age limit)
Evidence of a primary (e.g., not secondary to EVT of proximal vessel occlusion) distal medium vascular occlusion defined as occlusion of the M2 segment* or M3 segment of the MCA, the ACA (A1, A2, or A3 segments), or the PCA (P1, P2 or P3 segments) resulting in significant clinical deficits and expected to be treatable by endovascular thrombectomy. * M2 segment vessel diameter should not exceed 2.5 mm.
Premorbid mRS ≤ 2.
Evidence of a disabling stroke defined as follows:
Baseline National Institutes of Health Stroke Scale (NIHSS) score >5 at the time of randomization.
NIHSS score 3-5, with the following neurological deficits, including aphasia, hemianopsia or hemiplegia/loss of individual limb function, etc；.
Time from onset (or time last seen well) to randomization<12 hours；
For patients with more than 6 hours of onset (or time last seen well), the following conditions must be met: Target Mismatch Profile on CT perfusion or MRI (Mismatch Volume >10cc and mismatch Ratio >1.4 ).
Informed consent obtained from patient or acceptable patient surrogate.

Exclusion Criteria:

Any sign of intracranial hemorrhage on baseline CT/MR (SDH/SAH/ICH).
Rapidly improving symptoms, particularly if in the judgment of the managing clinician that the improvement is likely to result in the patient having an NIHSS score of <5 at randomization.
Significant ischemic changes in a territory other than the occluded site that in the opinion of the investigator could reduce the benefit of endovascular treatment.
Contra indication to imaging with MR or CT with contrast agents.
Infarct core >1/3 occluded territory (MCA, ACA, or PCA) qualitatively or >50 mL quantitatively (determined by CTP or DWI).
Any terminal illness such that patient would not be expected to survive more than 1 year.
Recent past history or clinical presentation of ICH, subarachnoid hemorrhage (SAH), arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm other than meningioma.
Any imaging findings suggestive of futile recanalization in the judgment of the local investigator.
seizures at stroke onset if it precludes obtaining an accurate baseline NIHSS.
Baseline blood glucose of <50 mg/dL (2.78 mmol) or >400 mg/dL (22.20 mmol).
Known history of hereditary or acquired hemorrhagic diathesis and/or platelet count <50×109/L.
Known renal failure as defined as serum creatinine levels > 260umol/l（3.0 mg/dL）.
Presumed septic embolus or suspicion of bacterial endocarditis.
Any other condition that, in the opinion of the investigator, precludes an endovascular procedure or poses a significant hazard to the subject if an endovascular procedure was performed.
History of drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
Subjects with occlusions in multiple vascular territories (e.g., bilateral or multi-territorial anterior circulation, or anterior/posterior circulation)
Subject participating in a study involving an investigational drug or device that would impact this study.
Known pregnancy.
Prisoner or incarceration