Clinical trial NCT04551664: Study of Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core
Official title: Study of Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core: A Multi-centered, Prospective, Open-label, Blind Endpoint， Randomized Controlled Trial（ANGEL-ASPECT）
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Ischemic Stroke
Keywords: endovascular therapy
large infarct volume
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2020-09-16
Enrollment: 456
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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
* Randomization can be finished within 24 hours of stroke onset (stroke onset time is defined as last known well time)
* Informed consent signed Specific Neuroimaging Inclusion Criteria
* CTA or MRA proved occlusion of Internal Carotid Artery (ICA) terminal or M1 segment of Middle Cerebral Artery
* Combination of NCCT ASPECTS and perfusion core volume when ASPECTS \<3 or \> 5 (6h-24h). Imaging evidence of low ASPECTS (based on NCCT) or large infarct Core (defined as rCBF \<30% on CT perfusion or ADC\<620 on MRI) filling one of the following criteria:

  1. ASPECTS 3-5
  2. ASPECTS \>5 (6h-24h) with infarct core volume 70-100 ml
  3. ASPECTS \<3 with infarct core volume 70-100 ml

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 tendency (including but not limited to): Baseline platelet count \<100×109/L; Heparin was administered within 48 hours with APTT≥35s; on anticoagulant therapy with warfarin and International Normalized Ratio (INR) \> 1.7 (Patients with no history or suspected coagulopathy do not need to wait for laboratory results of INR or APTT prior to enrollment)
* Parenchymal organ surgery and biopsy were performed in the past one month
* Any active bleeding or recent bleeding (gastrointestinal bleeding, urinary bleeding, etc.) in the past one month
* Undergoing hemodialysis or peritoneal dialysis; Known severe renal insufficiency with glomerular filtration rate \<30 ml/min or serum creatinine \>220 mmol/L (2.5mg/dl)
* Brain tumor (with mass effect)
* The expected survival time is less than 1 year (such as complicated with malignant tumor, serious heart and lung diseases, etc.)
* Participation in other interventional randomized clinical trials that may confound outcome assessment of the trial
* Other circumstances that the investigator considers inappropriate for participation in the trial or that may pose significant risks to patients (such as inability to understand and/or follow the study procedures and/or follow up due to mental disorders, cognitive or emotional disorders)

Specific Neuroimaging Exclusion Criteria

* Midline shift, herniation or mass effect with effacement of the ventricles
* Evidence of acute intracranial hemorrhage
* Acute bilateral strokes or multiple intracranial vessels occlusions

Primary outcomes:
measure: Neurofunctional deficit defined as modified Rankin Scale (mRS)
timeFrame: 90±7 days after randomization
Secondary outcomes:
measure: Rate of symptomatic intracranial hemorrhage (sICH) per Heidelberg standard
timeFrame: within 48 hours after randomization
measure: 90-day good clinical outcome
timeFrame: 90±14 days after randomization
measure: 90-day favorable clinical outcome
timeFrame: 90±7 days after randomization
measure: Dramatic recovery
timeFrame: baseline, 36±12 hours after randomization
measure: Change of infarct volume from baseline to 36-hour (24-48 hours)
timeFrame: baseline, 36±12 hours after randomization
measure: All-cause mortality rate
timeFrame: 90±7 days after randomization
measure: Any type of intracranial hemorrhage according to Heidelberg Classification.
timeFrame: 36±12 hours after randomization
measure: Rate of decompressive hemicraniectomy
timeFrame: 7±1 days after randomization or discharge
measure: Rate of successful recanalization
timeFrame: 36±12 hours after randomization
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital
state: Beijing
Study officials:
affiliation: Beijing Tiantan Hospital, Capital Medical Univerity
name: Zhongrong Miao, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: