Study of Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core
Study of Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core
Endovascular therapy (EVT) was recommended as the primary treatment for patients with acute
 large vascular occlusion (LVO) in anterior circulation. However, the evidences of EVT for
 patients with large infarct volume were limited. In this study, the investigators assume that
 best medical management plus EVT might be superior than best medical management alone for
 patients who have evidence of a large infarct volume. The primary objective of the study was
 to establish the safety and efficacy of EVT in patients presenting with symptoms of acute
 ischemic stroke (AIS) from LVO in the anterior circulation and having a large infarct volume.
The ANGEL-ASPECT is a multicentered, prospective, randomized, open-label, blinded end-point
 (PROBE) study. A total of approximately 488 patients (age from 18 to 80 years) within 24
 hours of symptom onset of acute ischemic stroke, who has the imaging evidence of an occlusion
 of the Internal Carotid Artery (ICA) terminus and/or Middle Cerebral Artery Main Stem (MCA
 M1) segment, large infarct core [ defined as: 1) NCCT (noncontrast computed tomography)
 ASPECTS (Alberta Stroke Program Early CT Score) 3-5, decided on last head CT scan before
 randomization. 2) Ischemic core volume ranges from 70-100ml, determined either on a
 diffusion-weighted MRI map based on an ADC (Apparent Diffusion Coefficient) threshold of less
 than 620 ×10-6mm2/s or on CTP (computed tomography perfusion) image with rCBF<30%] will be
 enrolled. Patients fulfilling all of the inclusion criteria and none of the exclusion
 criteria will be randomized 1:1 into two groups after offering informed content. One group
 will receive best medical management alone the other group will receive best medical
 management plus EVT including mechanical thrombectomy, aspiration thrombectomy,
 intra-arterial thrombolysis, angioplasty or stenting. The primary objective is to establish
 the efficacy of EVT in patients presenting with symptoms of acute ischemic stroke (AIS) from
 LVO in the anterior circulation and having a large infarct volume. The study consists of six
 visits including the day of randomization, 2 days after randomization, 7 days or discharge,
 and 30, 90 days and 1 year. Demographic information, symptoms and signs, laboratory test,
 neuro-imaging assessment neurological function rating scale will be recorded during the
 program. The primary endpoint is the modified Rankin's scale (mRS) at 90 days. The trial is
 anticipated to last from September 2020 to October 2022 with 488 subjects recruited form
 about 50 centers in China. All the related investigative organization and individuals will
 obey the Declaration of Helsinki and Chinese Good Clinical Practice standard. A Data and
 Safety Monitoring Board (DSMB) will regularly monitor safety during the study. The trial has
 been approved by Institutional Review Board (IRB) and Ethics Committee (EC) in Being Tiantan
 hospital, Capital Medical University.
Inclusion Criteria:

 General Inclusion Criteria

 -  18 to 80 years of age

 -  Presenting with symptoms consistent with an AIS

 -  Pre-stroke mRS score 0-1

 -  NIHSS score 6-30 at the time of randomization

 -  Ability to randomize within 24 hours of stroke onset

 -  Ability to obtain signed informed consent Specific Neuroimaging Inclusion Criteria

 -  Imaging evidence of an anterior circulation occlusion of the Internal Carotid Artery
 (ICA) terminus and/or Middle Cerebral Artery Main Stem (MCA M1) segment

 -  Imaging evidence of moderate-large infarct defined by either NCCT (ASPECTS: 3-5)
 advanced perfusion imaging ([rCBF<30%] on CTP or [ADC<620] on MRI: 70-100cc) (>6h/ <6h
 and ASPECT 0-2) or both.

 Exclusion Criteria:

 General Exclusion Criteria

 -  Females who are pregnant, or those of child-bearing potential with positive urine or
 serum beta Human Chorionic Gonadotropin (HCG) test;

 -  Known severe allergy (more than a rash) to contrast media uncontrolled by medications;

 -  Refractory hypertension (defined as persistent systolic blood pressure >185 mmHg or
 diastolic blood pressure >110 mmHg);

 -  Known hemorrhagic diathesis, coagulation factor deficiency, or on anticoagulant
 therapy with an International Normalized Ratio (INR) of >1.7 or Partial Thromboplastin
 Time (APTT) >35s; baseline platelet count <100X10^9/L;

 -  Biopsy of parenchymatous organs with 1 month

 -  Active bleeding within 1 month (such as gastrointestinal or urinary hemorrhage)

 -  Known severe renal failure (GFR <30ml/min or Scr>220mmol/L（2.5mg/dl）) or under the
 treatment of hematodialysis or peritoneal dialysis;

 -  Life expectancy less than 1 year prior to stroke onset (combined with malignant tumor,
 severe heart failure)

 -  All-cause acute intracranial hemorrhage or intracranial tumors with mass effect

 -  Participation in another randomized clinical trial that could confound the evaluation
 of the study

 -  Any other condition (in the opinion of the site investigator) that precludes an
 endovascular procedure or poses a significant hazard to the patient if an endovascular
 procedure was performed

 Specific Neuroimaging Exclusion Criteria

 -  Midline shift, herniation or mass effect with effacement of the ventricles

 -  Evidence of acute intracranial hemorrhage

 -  Bilateral strokes or multiple intracranial vessels occlusions