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

• ClinicalTrials.gov Identifier: NCT04551664
• Recruitment Status: Recruiting
• First Posted: September 16, 2020
• Last Update Posted: April 26, 2021
• Sponsor: Beijing Tiantan Hospital
• Information provided by (Responsible Party): Zhongrong Miao, Beijing Tiantan Hospital

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.

Condition or disease	Intervention/treatment	Phase
Acute Ischemic Stroke	Drug: Best medical management; Procedure: Endovascular therapy	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 488 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Health Services Research
• 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）
• Actual Study Start Date: October 2, 2020
• Estimated Primary Completion Date: January 2022
• Estimated Study Completion Date: November 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: EVT group; Patients in this group will receive best medical management plus EVT including mechanical thrombectomy, aspiration thrombectomy, intra-arterial thrombolysis, angioplasty or stenting.	Drug: Best medical management; 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.; Procedure: Endovascular therapy; 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.
Active Comparator: Best medical management group; Patients in this group will receive best medical management alone.	Drug: Best medical management; 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.

Outcome Measures

Primary Outcome Measures :

1. Neurofunctional deficit defined as modified Rankin Scale (mRS) [ Time Frame: 90±14 days after randomization ]

   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 :

1. Rate of symptomatic intracranial hemorrhage (sICH) per Heidelberg standard [ Time Frame: 36±12 hours after randomization ]

   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.

2. 90-day good clinical outcome [ Time Frame: 90±14 days after randomization ]
   Good clinical outcome defined as a dichotomized mRS 0-2 outcome
3. 90-day favorable clinical outcome [ Time Frame: 90±14 days after randomization ]
   Favorable clinical outcome defined as a dichotomized mRS 0-3 outcome
4. Dramatic recovery [ Time Frame: baseline, 36±12 hours after randomization ]
   36-hour (24-48 hours) NIHSS score ≤1 or ≥10 points drop as compared with baseline
5. Change of infarct volume from baseline to 36-hour (24-48 hours) [ Time Frame: baseline, 36±12 hours after randomization ]
   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%
6. All-cause mortality rate [ Time Frame: 90±14 days after randomization ]
   All-cause mortality rate at 90±14 days
7. Any type of intracranial hemorrhage according to Heidelberg Classification. [ Time Frame: 36±12 hours after randomization ]
   Any type of intracranial hemorrhage according to Heidelberg Classification.
8. Rate of decompressive hemicraniectomy [ Time Frame: 7 days after randomization or discharge ]
   Rate of decompressive hemicraniectomy
9. Rate of successful recanalization [ Time Frame: 36±12 hours after randomization ]
   Rate of participants with recanalization of the primary arterial occlusive lesion at 36±12 hours

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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
• 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

Contacts and Locations

Contacts

Contact: Xiaochuan Huo, MD; 86-1371629262; huoxiaochuan@126.com

Locations

China, Beijing

Beijing Tiantan Hospital; Recruiting

Beijing, Beijing, China, 100010

Contact: Zhongrong Miao, PhD,MD 13601243293 13601243293@163.com

Sponsors and Collaborators

Beijing Tiantan Hospital

Investigators

• Principal Investigator: Zhongrong Miao, MD, PhD; Beijing Tiantan Hospital, Capital Medical Univerity

More Information

• Responsible Party: Zhongrong Miao, Director of Department of interventional neurology, Beijing Tiantan Hospital
• ClinicalTrials.gov Identifier: NCT04551664
• Other Study ID Numbers: HX-A-011(2020)
• First Posted: September 16, 2020
• Last Update Posted: April 26, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Zhongrong Miao, Beijing Tiantan Hospital:

endovascular therapy; large infarct volume

Additional relevant MeSH terms:

Ischemic Stroke; Infarction; Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Ischemia; Pathologic Processes; Necrosis