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Study of Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core (ANGEL-ASPECT)

Primary Purpose

Acute Ischemic Stroke

Status

Completed

Phase

Not Applicable

Locations

China

Study Type

Interventional

Intervention

Best medical management

Endovascular therapy

About this trial

This is an interventional health services research trial for Acute Ischemic Stroke focused on measuring endovascular therapy, large infarct volume

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Beijing Tiantan Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

EVT group

Best medical management group

Arm Description

Patients in this group will receive best medical management plus EVT including mechanical thrombectomy, aspiration thrombectomy, intra-arterial thrombolysis, angioplasty or stenting.

Patients in this group will receive best medical management alone.

Outcomes

Primary Outcome Measures

Neurofunctional deficit defined as modified Rankin Scale (mRS)

The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6 with "0" being perfect health without symptoms to "6" being death. Score 0: No symptoms Score 1: No significant disability. Able to carry out all usual activities, despite some symptoms. Score 2: Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. Score 3: Moderate disability. Requires some help, but able to walk unassisted. Score 4: Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. Score 5: Severe disability. Requires constant nursing care and attention, bedridden, incontinent. Score 6: Dead

Secondary Outcome Measures

Rate of symptomatic intracranial hemorrhage (sICH) per Heidelberg standard

Heidelberg standard was defined as new intracranial hemorrhage detected by brain imaging associated with any of the item below: 4 points total NIHSS at the time of diagnosis compared to immediately before worsening. 2 point in one NIHSS category. Leading to intubation/hemicraniectomy/ventricular drainage placement or other major medical/surgical intervention. Absence of alternative explanation for deterioration.

90-day good clinical outcome

Good clinical outcome defined as a dichotomized mRS 0-2 outcome

90-day favorable clinical outcome

Favorable clinical outcome defined as a dichotomized mRS 0-3 outcome

Dramatic recovery

36-hour (24-48 hours) NIHSS score ≤1 or ≥10 points drop as compared with baseline

Change of infarct volume from baseline to 36-hour (24-48 hours)

The infarct volume is determined on a diffusion-weighted MRI map based on an ADC threshold of less than 620 ×10-6mm2/s or on CTP image with rCBF<30%

All-cause mortality rate

All-cause mortality rate at 90±14 days

Any type of intracranial hemorrhage according to Heidelberg Classification.

Rate of decompressive hemicraniectomy

Rate of successful recanalization

Rate of participants with recanalization of the primary arterial occlusive lesion at 36±12 hours

Full Information

NCT ID

NCT04551664

First Posted

September 10, 2020

Last Updated

October 16, 2023

Sponsor

Beijing Tiantan Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04551664

Brief Title

Study of Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core

Acronym

ANGEL-ASPECT

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

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Completed

Study Start Date

October 2, 2020 (Actual)

Primary Completion Date

August 15, 2022 (Actual)

Study Completion Date

May 30, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Beijing Tiantan Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Ischemic Stroke

Keywords

endovascular therapy, large infarct volume

7. Study Design

Primary Purpose

Health Services Research

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

456 (Actual)

8. Arms, Groups, and Interventions

Arm Title

EVT group

Arm Type

Experimental

Arm Description

Patients in this group will receive best medical management plus EVT including mechanical thrombectomy, aspiration thrombectomy, intra-arterial thrombolysis, angioplasty or stenting.

Arm Title

Best medical management group

Arm Type

Active Comparator

Arm Description

Patients in this group will receive best medical management alone.

Intervention Type

Drug

Intervention Name(s)

Best medical management

Intervention Description

All the patients enrolled received standard guideline-directed medical therapy including: monitor vital signs, management of blood pressure, glucose and lipids, antithrombotic (antiplatelet or anticoagulant therapy determined by treating physician) therapy if appropriate.

Intervention Type

Procedure

Intervention Name(s)

Endovascular therapy

Intervention Description

In the procedure, the methods including mechanical thrombectomy, aspiration thrombectomy, intra-arterial thrombolysis, angioplasty and stenting can be used according to the local interventionalists' choice. Mechanical thrombectomy (recommended with Solitaire、EMBOTRAP、Trevo or Reco revascularization device) or aspiration thrombectomy (recommended with Penumbra) will be recommended as the primary treatment.

Primary Outcome Measure Information:

Title

Neurofunctional deficit defined as modified Rankin Scale (mRS)

Description

Time Frame

90±7 days after randomization

Secondary Outcome Measure Information:

Title

Rate of symptomatic intracranial hemorrhage (sICH) per Heidelberg standard

Description

Time Frame

within 48 hours after randomization

Title

90-day good clinical outcome

Description

Good clinical outcome defined as a dichotomized mRS 0-2 outcome

Time Frame

90±14 days after randomization

Title

90-day favorable clinical outcome

Description

Favorable clinical outcome defined as a dichotomized mRS 0-3 outcome

Time Frame

90±7 days after randomization

Title

Dramatic recovery

Description

36-hour (24-48 hours) NIHSS score ≤1 or ≥10 points drop as compared with baseline

Time Frame

baseline, 36±12 hours after randomization

Title

Change of infarct volume from baseline to 36-hour (24-48 hours)

Description

The infarct volume is determined on a diffusion-weighted MRI map based on an ADC threshold of less than 620 ×10-6mm2/s or on CTP image with rCBF<30%

Time Frame

baseline, 36±12 hours after randomization

Title

All-cause mortality rate

Description

All-cause mortality rate at 90±14 days

Time Frame

90±7 days after randomization

Title

Any type of intracranial hemorrhage according to Heidelberg Classification.

Description

Any type of intracranial hemorrhage according to Heidelberg Classification.

Time Frame

36±12 hours after randomization

Title

Rate of decompressive hemicraniectomy

Description

Rate of decompressive hemicraniectomy

Time Frame

7±1 days after randomization or discharge

Title

Rate of successful recanalization

Description

Rate of participants with recanalization of the primary arterial occlusive lesion at 36±12 hours

Time Frame

36±12 hours after randomization

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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: ASPECTS 3-5 ASPECTS >5 (6h-24h) with infarct core volume 70-100 ml 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zhongrong Miao, MD, PhD

Organizational Affiliation

Beijing Tiantan Hospital, Capital Medical Univerity

Official's Role

Principal Investigator

Facility Information:

Facility Name

Beijing Tiantan Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100010

Country

China

12. IPD Sharing Statement

Plan to Share IPD

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Study of Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core

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