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

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

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 co/non-dominant 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.

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke; Endovascular Thrombectomy
• Intervention / Treatment: Procedure: endovascular treatment; Other: Standard medical management

• Study Type: Interventional
• Enrollment (Estimated): 564
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wei Hu, MD, PhD; Phone Number: +86 055162284313; Email: andinghu@ustc.edu.cn

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230001
      • Recruiting
      • The First Affiliated Hospital of University of Science and Technology of China
      • Contact: Wei Hu, MD; Phone Number: +8615155510611; Email: andinghu@ustc.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years (no upper age limit).

2. Evidence of a primary (e.g., not secondary to EVT of proximal vessel occlusion) distal medium vascular occlusion defined as occlusion of the co/non-dominant 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.

   * Co/non-dominant M2 segment vessel diameter should not exceed 2.0 mm. Co-dominant supplying 50% of the MCA territory vs non-dominant supplying <50% of the MCA territory.

3. Premorbid mRS ≤ 2.
4. Baseline National Institutes of Health Stroke Scale (NIHSS) score ≥6 at the time of randomization.
5. Time from onset (or time last seen well) to randomization<12 hours.

6. For patients with more than 6 hours of onset (or time last seen well), Clinical-Imaging mismatch assessment defined as any of the following scenarios (A or B):

   A. Non-contrast CT of the head or Brain MRI DWI lesion with <50% involvement of the vascular territory corresponding to the clinical manifestation:

   B. Target Mismatch Profile on CT perfusion or MRI (Mismatch Volume >10cc and mismatch Ratio >1.4 ).

7. Informed consent obtained from patient or acceptable patient surrogate.

Exclusion Criteria:

1. Any sign of intracranial hemorrhage on baseline CT/MR (SDH/SAH/ICH).
2. 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 <6 at randomization.
3. 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.
4. Contra indication to imaging with MR or CT with contrast agents.
5. Any terminal illness such that patient would not be expected to survive more than 1 year.
6. Recent past history or clinical presentation of ICH, subarachnoid hemorrhage (SAH), arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm other than meningioma.
7. Any imaging findings suggestive of futile recanalization in the judgment of the local investigator.
8. seizures at stroke onset if it precludes obtaining an accurate baseline NIHSS.
9. Baseline blood glucose of <50 mg/dL (2.78 mmol) or >400 mg/dL (22.20 mmol).
10. Known history of hereditary or acquired hemorrhagic diathesis and/or platelet count <50×109/L.
11. Known renal failure as defined as serum creatinine levels > 260umol/l（3.0 mg/dL）.
12. Presumed septic embolus or suspicion of bacterial endocarditis.
13. 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.
14. History of drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
15. Subjects with occlusions in multiple vascular territories (e.g., bilateral or multi-territorial anterior circulation, or anterior/posterior circulation)
16. Subject participating in a study involving an investigational drug or device that would impact this study.
17. Known pregnancy.
18. Prisoner or incarceration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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	Other: Standard medical management; Standard medical management

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The 90-day modified Rankin Scale (mRS)	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.	90 (± 14 days) after procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale (mRS)	Shift in distribution of the 90-day mRS (0;1;2;3;4;5;6) as assessed by structured assessment.	90 (± 14 days) after procedure
Independent Outcome	Rates of Independent Outcome defined as mRS ≤2 and/ or equal to Baseline mRS at 90 days	90 (± 14 days) after procedure
Excellent Outcome	Rates of Excellent Outcome defined as mRS ≤1 and/ or equal to Baseline mRS at 90 days	90 (± 14 days) after procedure
Good Functional Outcomes	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	90 (± 14 days) after procedure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Number of subjects who died at 90-day follow-up/total number of subjects who participated in 90-day follow-up) x100%	90 (± 14 days) after procedure
Symptomatic intracranial hemorrhage (SICH)	SICH means any hemorrhage with neurological deterioration, as indicated by an NIHSS score that was higher by ≥4 points than the value at baseline or the lowest value in the first 24 hours (-2/+12) , or any hemorrhage leading to death.	24 hours (-2/+12H) after procedure

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of University of Science and Technology of China
• Investigators: Study Chair: Wei Hu, MD, PhD, The First Affiliated Hospital of University of Science and Technology of China

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: November 10, 2023
• First Submitted That Met QC Criteria: November 18, 2023
• First Posted (Actual): November 27, 2023

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 25, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Endovascular Treatment; Standard Medical Management; Medium Vessel Occlusion; Stroke Due To Medium Vessel Occlusion
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: ORIENTAL-MeVO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No