Acute Ischemic Stroke, Intracranial Atherosclerosis ICAS
Conditions
Keywords
Intracranial Atherosclerotic Disease, Large Vessel Occlusion, Residual Intracranial Stenosis, Rescue Balloon Angioplasty, Intracranial Stenting, Endovascular Thrombectomy
Brief summary
The ANGEL-ICAS trial is a multicenter, prospective, randomized, open-label, blinded-endpoint study designed to determine whether rescue balloon angioplasty is noninferior to rescue stenting in patients with intracranial atherosclerosis-related acute ischemic stroke who have residual intracranial arterial stenosis of at least 50% after endovascular treatment and require additional rescue therapy. A total of 486 eligible participants will be randomly assigned in a 1:1 ratio to the balloon angioplasty group or the stenting group. In the balloon angioplasty group, rescue stenting is permitted if the angiographic result after balloon angioplasty is considered inadequate. In the stenting group, balloon angioplasty may be performed in conjunction with stent implantation when clinically indicated. Both groups will receive standard medical management according to the study protocol. The primary outcome is the proportion of participants achieving functional independence, defined as a modified Rankin Scale score of 0-2, at 90 days after randomization. Key safety outcomes include symptomatic intracranial hemorrhage within 48 hours, any intracranial hemorrhage within 48 hours, and all-cause mortality at 90 days
Interventions
PROCEDUREballoon angioplasty
Balloon angioplasty treatment followed by standard medical therapy post-procedure.
PROCEDUREStent
Patients will receive either balloon-assisted stenting or direct stenting, followed by standard medical therapy after the endovascular treatment.
Sponsors
Beijing Anzhen Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Participants and treating interventionists will be aware of treatment allocation. Clinical outcome assessors, personnel conducting the 90-day follow-up, and central imaging core laboratory readers will remain blinded to treatment allocation and the treatment actually received. Imaging outcomes will be assessed independently using centralized blinded evaluation.
Intervention model description
Eligible participants will be centrally randomized in a 1:1 ratio to rescue balloon angioplasty or rescue stenting in parallel. Randomization will be performed using a stratified block design, with stratification by participating center and target-vessel occlusion location. The study is designed to evaluate the noninferiority of rescue balloon angioplasty to rescue stenting for the primary outcome.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years or older. 2. Pre-stroke modified Rankin Scale (mRS) score of 0-1. 3. Symptoms of acute ischemic stroke presenting within 24 hours of the last known well time. 4. Baseline National Institutes of Health Stroke Scale (NIHSS) score of at least 6. 5. Baseline Alberta Stroke Program Early CT Score (ASPECTS) of at least 6 for anterior-circulation stroke, or posterior-circulation ASPECTS (pc-ASPECTS) of at least 6 for posterior-circulation stroke. 6. Occlusion of the intracranial internal carotid artery, M1 segment of the middle cerebral artery, V4 segment of the vertebral artery, or basilar artery. 7. The clinical care team plans to perform endovascular treatment. 8. The participant or the participant's legally authorized representative is able to provide written informed consent. 9. Baseline CT perfusion or MR perfusion imaging demonstrating an ischemic core volume of less than 70 mL, a mismatch ratio of at least 1.2, and a mismatch volume of at least 15 mL. 10. Intracranial atherosclerosis is considered the underlying etiology, with residual stenosis of at least 50% after endovascular treatment, and rescue balloon angioplasty or stenting is planned
Exclusion criteria
1. Any intracranial hemorrhage identified on imaging before randomization; or major intracranial hemorrhage, defined as parenchymal hematoma type 1 or type 2, identified on intraprocedural flat-panel CT. Parenchymal hematoma type 1 is defined as blood clots involving less than 30% of the infarcted area, with or without a slight space-occupying effect; parenchymal hematoma type 2 is defined as blood clots involving more than 30% of the infarcted area with a substantial space-occupying effect. 2. Gastrointestinal or genitourinary bleeding within 30 days before stroke onset, or major surgery within 14 days before stroke onset. 3. Bleeding diathesis, including platelet count below 100 × 10⁹/L, activated partial thromboplastin time greater than 50 seconds, or international normalized ratio greater than 2.0; treatment with a direct oral anticoagulant within the preceding 48 hours; or a history of heparin-induced thrombocytopenia. 4. Pregnancy or breastfeeding at admission. 5. Contraindication to iodinated contrast agents, nickel, titanium, or their alloys. 6. Life expectancy of less than 6 months. 7. Pre-existing neurological or psychiatric disease that may confound neurological or functional outcome assessment. 8. Severe renal impairment, defined as glomerular filtration rate below 30 mL/min or serum creatinine above 220 μmol/L (2.5 mg/dL). 9. Arterial tortuosity or another arterial condition that would prevent the study device from reaching the target vessel. 10. Unlikely to complete the 90-day follow-up. 11. Any definite cardioembolic source, including chronic or paroxysmal atrial fibrillation, sick sinus syndrome, mitral stenosis, mechanical heart valve, endocarditis, history of atrial or ventricular thrombus, myocardial infarction within the preceding 3 months, dilated cardiomyopathy, spontaneous echo contrast in the left atrium, or left ventricular ejection fraction below 30%. 12. Use of any glycoprotein IIb/IIIa inhibitor other than tirofiban.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with mRS 0-2 | 90 days after randomization (±7 days) | Functional independence is defined as a modified Rankin Scale (mRS) score of 0-2. The mRS is an ordinal scale ranging from 0 (no symptoms) to 6 (death), with lower scores indicating better functional outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in NIHSS Score From Baseline to 36 Hours | 36 hours after randomization (±12 hours) | The National Institutes of Health Stroke Scale (NIHSS) ranges from 0 to 42, with higher scores indicating greater neurological impairment. Change will be calculated as the NIHSS score at 36 hours minus the baseline NIHSS score; negative values indicate neurological improvement. |
| Change in Infarct Volume From Baseline to Day 7 or Discharge | 7 days after randomization (±1 day) or at discharge, whichever occurs first | Change in infarct volume will be calculated as the follow-up infarct volume minus the baseline ischemic core volume, measured in milliliters by the blinded central imaging core laboratory using validated automated imaging software. Positive values indicate infarct growth. |
| Distribution of mRS Scores at Day 7 or Discharge | 7 days after randomization or at discharge, whichever occurs first | Distribution of modified Rankin Scale scores across all categories from 0 (no symptoms) to 6 (death), with lower scores indicating better functional outcomes. |
| Distribution of mRS Scores at 90 Days | 90 days after randomization (±7 days) | Distribution of modified Rankin Scale scores across all categories from 0 (no symptoms) to 6 (death), with lower scores indicating better functional outcomes. |
| Proportion of Participants Achieving an Excellent Functional Outcome at 90 Days | 90 days after randomization (±7 days) | An excellent functional outcome is defined as a modified Rankin Scale score of 0-1. The mRS ranges from 0 (no symptoms) to 6 (death). |
| Proportion of Participants With an mRS Score of 0-3 at 90 Days | 90 days after randomization (±7 days) | The outcome is defined as a modified Rankin Scale score of 0-3. The mRS ranges from 0 (no symptoms) to 6 (death), with lower scores indicating better functional outcomes. |
| Proportion of Participants Requiring Additional Pharmacologic Rescue Therapy | Within 90 days after randomization | Proportion of participants who receive additional pharmacologic rescue treatment for target-vessel reocclusion, restenosis, or related clinical deterioration after the randomized intervention. Protocol-mandated routine antiplatelet treatment will not be counted as pharmacologic rescue therapy. |
| Proportion of Participants Requiring Additional Procedural Rescue Treatment | Within 90 days after randomization | Proportion of participants who undergo an additional endovascular or surgical rescue procedure because of target-vessel reocclusion, restenosis, or related clinical deterioration after the randomized intervention. |
| EQ-5D-5L Index Score at 90 Days | 90 days after randomization (±7 days) | Health-related quality of life will be assessed using the EQ-5D-5L index score calculated with the prespecified Chinese value set. Scores range from -0.594 to 1.000, with higher scores indicating better health status. |
| Symptomatic Intracranial Hemorrhage Within 48 Hours | Within 48 hours after randomization | Symptomatic intracranial hemorrhage will be classified according to the Heidelberg Bleeding Classification and adjudicated by the blinded central imaging core laboratory and clinical event assessors. |
| All-Cause Mortality at 90 Days | Within 90 days after randomization (assessment window ±7 days) | Proportion of participants who die from any cause within 90 days after randomization. |
| Proportion of Participants With Target-Vessel Recanalization at 36 Hours | 36 hours after randomization (±12 hours) | Target-vessel recanalization will be assessed on CT angiography or MR angiography by the blinded central imaging core laboratory according to the prespecified imaging criterion. |
| Any Intracranial Hemorrhage Within 48 Hours | Within 48 hours after randomization | Any intracranial hemorrhage identified on follow-up CT or MRI and classified according to the Heidelberg Bleeding Classification, irrespective of the presence of neurological deterioration. |
Countries
China
Contacts
CONTACTXiaochuan Huo, Doctor
CONTACTXin Tong, Doctor
Outcome results
None listed