Acute Ischemic Stroke
Conditions
Keywords
Acute ischemic stroke, Tirofiban, Large vessel occlusion, Intracranial atherosclerotic disease, bridging treatment
Brief summary
The investigators propose to assess the efficacy and safety of intravenous tirofiban after bridging therapy (endovascular therapy \[EVT\] following intravenous Tenecteplase) for acute ischemic stroke due to intracranial atherosclerotic disease related large vessel occlusion (ICAD related LVO). This study will recruit 564 patients from about 50 hospitals in China. Inclusion criteria for the trial are: (1)age ≥18 years old, (2)Pre-mRS 0-2, (3)Baseline NIHSS 6-30 points, (4) Baseline ASPECTS ≥6 points, (5) Baseline CTA/MRA diagnosed: the ICA or MCA-M1/M2 occlusion, (6) Receiving bridging therapy (EVT following IV Tenecteplase) within 24 hours from stroke onset (7) Baseline DSA diagnosed: ICAD related LVO(if any one the following criteria is fulfilled: 1) absence of atrial fibrillation; 2) truncal-type occlusion; 3) residual stenosis ≥30% on DSA after the first retriever; 4) researchers determined it to be ICAD-related LVO based on the TOAST classification, (8) Have achieved successful reperfusion after EVT (mTICI ≥2b). Patients with previously known permanent, persistent, or paroxysmal atrial fibrillation, permanent stenting during EVT, severe bleeding or had a higher bleeding risk in the last 6 months, imaging examination before randomization showed the Heidelberg hemorrhage type 1c, 2, or 3 ICH with or without clinical exacerbation, infarct area greater than 50% of the middle cerebral artery blood supply area or infarct volume ≥70ml, cerebral hernia signs, and some other severe organic diseases and an expected survival time of less than 90 days, severe liver insufficiency or renal insufficiency will be excluded. Patients will be randomly assigned to the experimental group or control group at a 1:1 ratio. Experimental group will receive intravenous tirofiban of a dose of 0.4 μg/kilo/min for 30 minutes after the completion of bridging therapy, followed by a continuous infusion of 0.1 μg/kilo/min for up to 24 hours. Then the patient will transition to standard medical therapy, with no restrictions on the antiplatelet regimen but is advised to receive loading dose dual antiplatelet therapy (oral aspirin 100 mg and clopidogrel 300 mg four hours before the end of intravenous tirofiban and daily oral aspirin 100 mg and clopidogrel 75 mg for 30 days). Control group will receive standard medical therapy after bridging treatment. The primary endpoint is the proportion of modified Rankin Scale (mRS) score 0 to 2 at 90±7 days after onset. The primary safety outcome is the symptomatic intracerebral hemorrhage (sICH) within 48 hours after randomization according to ECASS III criteria. This trial will provide important information for the standardization of antiplatelet medication regimens after bridging therapy for improving functional outcomes in patients with acute large vessel atherosclerotic occlusive ischemic stroke.
Interventions
DRUGIntravenous Tirofiban
Intravenous infusion of tirofiban within 5 minutes after randomization at a dose of 0.4 μg/kg/min for 30 minutes, followed by maintenance infusion via an intravenous microinfusion pump at 0.1 μg/kg/min for 23.5 hours (if tirofiban has already been administered intraoperatively, a continuous intravenous microinfusion pump at 0.1 μg/kg/min will be started directly postoperatively and continued for 24 hours). Tirofiban will be discontinued at 24 hours.
DRUGStandard Medical Therapy
standard medical therapy after randomization. The antiplatelet regimen is not restricted.
Sponsors
Beijing Tiantan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients will be randomly assigned to the experimental group or control group at a 1:1 ratio. Experimental group: will receive intravenous infusion of tirofiban within 5 minutes after randomization at a dose of 0.4 μg/kg/min for 30 minutes, followed by maintenance infusion via an intravenous microinfusion pump at 0.1 μg/kg/min for 23.5 hours (if tirofiban has already been administered intraoperatively, a continuous intravenous microinfusion pump at 0.1 μg/kg/min will be started directly postoperatively and continued for 24 hours). Tirofiban will be discontinued at 24 hours. Control group: will receive standard medical therapy after bridging treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years old. 2. Pre-mRS 0-2. 3. Baseline NIHSS 6-30 points. 4. Baseline ASPECTS ≥6 points. 5. Baseline CTA/MRA diagnosed: the ICA or MCA-M1/M2 occlusion. 6. Receiving bridging therapy (EVT following IV Tenecteplase) within 24 hours from stroke onset. 7. Baseline DSA diagnosed: ICAD related LVO. \* ICAD-related LVO is assumed if any one the following criteria is fulfilled: (1) absence of atrial fibrillation; (2) truncal-type occlusion; (3) residual stenosis ≥30% on DSA after the first retriever; (4) researchers determined it to be ICAD-related LVO based on the TOAST classification. 8. Patients have achieved successful reperfusion after EVT (mTICI ≥2b). 9. Patients or their eligible surrogates provided informed consent.
Exclusion criteria
1. Previously known permanent, persistent, or paroxysmal atrial fibrillation. 2. Permanent stenting during EVT; 3. Patient had severe bleeding or the following conditions, such as active gastrointestinal ulcer, aortic dissection, platelet count \<100 ×109/L, hemoglobin \<100 g/L, INR≥1.7 in the last 6 months. 4. Contraindication to glycoprotein IIb/IIIa inhibitors. 5. Imaging examination (Flat-panel NCCT/DCT) before randomization showed the following: Heidelberg hemorrhage type 1c, 2, or 3 ICH with or without clinical exacerbation (an increase of ≥4 points in the NIHSS score from baseline or an increase of ≥2 points in any of the NIHSS scores or resulting in intubation, decompression of bone valves, ventricular drainage, or other significant medical/surgical intervention), infarct area greater than 50% of the middle cerebral artery blood supply area or infarct volume ≥70ml, cerebral hernia signs. 6. Vascular malformations, arterial dissection, intracranial aneurysms, tumors (except for small meningiomas), cerebrovascular inflammation, cerebral amyloid angiopathy, or other major non-ischemic craniocerebral diseases (e.g. multiple sclerosis) as diagnosed by head imaging. 7. Acute renal failure, dialysis, or estimated glomerular filtration rate (eGFR) \< 30ml/min/1.72m2, or serum creatinine \> 220mmol/L (2.5mg/dl). 8. History of severe liver disease, or aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/or glutamyltransferase (GGT) ≥3×ULN and/or total bilirubin (TBIL) ≥2×ULN. 9. Acute ST elevation myocardial infarction (MI), acute decompensated heart failure, QTc\>500 ms, hospitalization or involuntary coronary intervention due to acute coronary syndrome, MI, cardiac arrest within the past 3 months. 10. Severe non-cardiovascular comorbidity with life expectancy \< 3 months (e.g., malignant tumors). 11. Any clinical conditions determined by the study team that may limit adherence to the study process. 12. Currently receiving an investigational drug or device. 13. Women of childbearing age not practicing reliable contraception who do not have a documented negative pregnancy test. 14. The subject's informed consent was not obtained.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the proportion of mRS score 0 to 2 | at 90±7 days after onset | The modified Rankin scale is a measure of disability, with scores ranging from 0 (no symptoms) to 6 (death), with 0 indicating no symptoms at all; 1 indicating no significant disability despite symptoms: able to carry out all usual duties and activities, 2 indicating slight disability: unable to carry out all previous activities but able to look after own affairs without assistance. |
| symptomatic intracerebral hemorrhage according to ECASS III criteria | within 48 hours after randomization | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| mRS score 0 to 3 | at 90±7 days after onset | The modified Rankin scale is a measure of disability, with scores ranging from 0 (no symptoms) to 6 (death), with 0 indicating no symptoms at all; 1 indicating no significant disability despite symptoms: able to carry out all usual duties and activities, 2 indicating slight disability: unable to carry out all previous activities but able to look after own affairs without assistance; 3 indicating moderate disability: requiring some help, but able to walk without assistance. |
| Early reocclusion | within 48±12 hours after randomization | — |
| Severe bleeding according to GUSTO criteria | within 48±12 hours after randomization | — |
| Ordinal mRS score | at 90±7 days after onset | The modified Rankin scale is a measure of disability, with scores ranging from 0 (no symptoms) to 6 (death), with 0 indicating no symptoms at all; 1 indicating no significant disability despite symptoms: able to carry out all usual duties and activities, 2 indicating slight disability: unable to carry out all previous activities but able to look after own affairs without assistance; 3 indicating moderate disability: requiring some help, but able to walk without assistance; 4 indicating moderately severe disability: unable to walk without assistance, and unable to attend to own bodily needs without assistance; 5 indicating severe disability: bedridden, incontinent, and requiring constant nursing care and attention; and 6 indicating death. |
| Any intracerebral hemorrhage | within 48±12 hours after randomization | — |
| Mortality | within 90 days after onset | — |
| Early neurological deterioration (increase in NIHSS score ≥4 points within 72 hours after randomization) | within 72±12 hours after randomization | — |
| mRS score 0 to 1 | at 90±7 days after onset | The modified Rankin scale is a measure of disability, with scores ranging from 0 (no symptoms) to 6 (death), with 0 indicating no symptoms at all; 1 indicating no significant disability despite symptoms: able to carry out all usual duties and activities. |
Countries
China
Contacts
Primary ContactLiping Liu
Outcome results
None listed