Acute Ischemic Stroke
Conditions
Keywords
Acute Ischemic Stroke, thrombolysis, Tirofiban
Brief summary
A multicenter, double-blind, double-dummy, randomized trial evaluating the efficacy and safety of intravenous tirofiban in acute ischemic stroke (AIS) patients without large/medium vessel occlusion, who presented 4.5-24 hours after onset and received intravenous thrombolysis (IVT).
Detailed description
This study is a multicenter, double-blind, double-dummy, randomized clinical trial designed to evaluate the efficacy and safety of intravenous tirofiban in acute ischemic stroke (AIS) patients without large/medium vessel occlusion, who presented 4.5-24 hours after onset and received intravenous thrombolysis (IVT). The primary outcome is the proportion of patients with a 90-day modified Rankin scale (mRS) of 0-1. Study intervention: (1) Participants in the intervention group will receive intravenous tirofiban as soon as possible after the randomization. (2) Participants in the control group will receive matched intravenous placebo in the same approach. All participants will receive standard medical treatment. A total of 852 participants are anticipated to be recruited for this study, with 426 participants in each group (1:1 ratio).
Interventions
DRUGTirofiban
Tirofiban is administered as a loading dose and continuous intravenous infusion as soon as possible after the randomization.
DRUGPlacebo
Matched placebo will be infused in a similar fashion.
Sponsors
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged 18 years or older; 2. Clinical diagnosed acute ischemic stroke (AIS) with last known well time of 4.5-24 hours; 3. Any of the following presentation of AIS: 1\) Treated with IVT followed by no significant change in neurological function; 2) Treated with IVT followed by early neurological deterioration; 4. NIHSS score ≥4 before randomization; 5. Able to receive the designated study drug within 60 minutes after IVT; 6. Written informed consent is obtained from patients and/or their legal representatives.
Exclusion criteria
1. Intracranial or subarachnoid hemorrhage confirmed by cranial computed tomography (CT) or magnetic resonance imaging (MRI), or any intracranial hemorrhage history; 2. CTA/MRA/DSA showed occlusion of the internal carotid artery, middle cerebral artery M1 or M2 segment, anterior cerebral artery A1 segment, and vertebrobasilar artery; 3. Presence of any of the following unequivocal cardiac sources of embolism: chronic or paroxysmal atrial fibrillation, sick sinus syndrome, mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation, myocardial infarction within three months, dilated cardiomyopathy, left atrial spontaneous echo contrast, ejection fraction less than 30%; 4. Pre-stroke modified Rankin scale (mRS)≥2; 5. Renal insufficiency (glomerular filtration rate \< 30 mL/min or serum creatinine \> 220 μmol/L \[2.5 mg/dl\]); 6. Pregnant or lactating women; 7. NCCT, CTA source imaging, or MRI-DWI showing ASPECTS or PC-ASPECTS \< 6; 8. Allergy to tirofiban, other glycoprotein IIb/IIIa inhibitors, aspirin or clopidogrel; 9. History of bleeding disorder, severe heart, liver or kidney disease, or sepsis; 10. Active bleeding diathesis, including clinical laboratory evidence of coagulation abnormalities (platelet count \< 100×10⁹/L, activated partial thromboplastin time \>50 seconds or international normalized ratio \> 1.7), or treatment with a direct oral anticoagulant within the prior 48h; 11. CT or MR evidence of mass effect or intracranial tumor (except small meningioma); 12. CT or MR angiography evidence of intracranial arteriovenous malformations or aneurysm; 13. Severe allergy to contrast agents (non-mild rash allergy) or absolute contraindication to iodine contrast; 14. Any terminal illness with life expectancy less than 6 months; 15. Participating in other clinical trials; 16. Other conditions deemed unsuitable for the study by the investigator, such as inability to comprehend or comply with study procedures or follow-up due to mental illness, cognitive or emotional disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The modified Rankin Scale score (mRS) 0-1 | 90 (±14) days | The proportion of mRS score 0-1 at 90 (±14) days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distribution of modified Rankin Scale score at 90 days | 90 (±14) days | The shift analysis of the 90-day mRS with 5-6 merged at 90 (±14) days. |
| The modified Rankin Scale score 0-2 | 90 (±14) days | The proportion of mRS score 0-2 at 90 (±14) days. |
| Early neurological improvement | 48 (±12) hours | The proportion of patients with a ≥30% decrease in National Institute of Health stroke scale score from baseline. |
| Quality of life (EQ-5D-5L) | 90 (±14) days | Health-related quality of life measured by EQ-5D-5L scale score at 90 (±14) days. |
Other
| Measure | Time frame | Description |
|---|---|---|
| SAFETY OUTCOME: Any intracranial hemorrhage | 48 (±12) hours | Rate of any intracranial hemorrhage within 48 hours from randomization |
| SAFETY OUTCOME: Major extracranial bleeding | 48 (±12) hours | Rate of major extracranial bleeding within 48 hours from randomization (as defined by the Global Utilization of Streptokinase and Tissue-type Plasminogen Activator for Occluded Coronary Arteries, GUSTO criteria: moderate and severe bleeding) |
| SAFETY OUTCOME: Mortality | 90(±14) days | All-cause mortality within 90 days. |
| SAFETY OUTCOME: Symptomatic intracranial hemorrhage | 48 (±12) hours | Rate of symptomatic intracranial hemorrhage (sICH) within 48 hours from randomization (Heidelberg bleeding classification) |
Countries
China
Contacts
Primary ContactJinyuan Wang
Backup ContactXinguang Yang
Outcome results
None listed