Adding intravenous tirofiban after clot-busting treatment for patients who don't improve quickly from acute ischemic stroke

Intravenous Thrombolysis Combined With Tirofiban in Acute Ischemic Stroke: A Multicenter, Prospective, Double-Blind, Placebo-Controlled, Randomized Controlled Trial

This trial will test whether giving the IV medicine tirofiban after standard clot-busting treatment helps adults with acute ischemic stroke who show poor improvement within an hour.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 976 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Beijing Anzhen Hospital (Academic / other)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07290751 on ClinicalTrials.gov

What this trial studies

ANGEL-DRUG2 is a multicenter, double-blind, placebo-controlled randomized trial enrolling about 976 patients who received intravenous thrombolysis within 4.5 hours but showed insufficient neurological improvement at 1 hour. Participants are randomized 1:1 to a 24-hour tirofiban infusion (loading then maintenance dose) or matching placebo, with transition to standard oral antiplatelet therapy during the infusion. The primary outcome is functional independence (mRS 0-2) at 90 days, and secondary outcomes include NIHSS change, vessel recanalization, infarct volume, recurrent stroke, and quality of life. Safety monitoring focuses on symptomatic intracranial hemorrhage and all-cause mortality.

Who should consider this trial

Good fit: Adults aged 18 or older with pre-stroke mRS 0-1 who received IV thrombolysis within 4.5 hours, have baseline NIHSS ≥4, and show poor or worsening neurological improvement one hour after thrombolysis without plans for endovascular therapy are ideal candidates.

Not a fit: Patients with intracranial hemorrhage on imaging, those needing thrombectomy for large or medium vessel occlusion, or those with contraindications to tirofiban are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could increase the chance of functional independence at 90 days for patients who fail to improve after initial thrombolysis.

How similar studies have performed: Smaller trials and observational studies and some EVT-associated data have suggested tirofiban may help reduce platelet aggregation without large increases in symptomatic intracranial hemorrhage, but high-quality randomized evidence in this specific post-thrombolysis poor-response group is limited.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years.
2. Pre-stroke modified Rankin Scale (mRS) score of 0-1.
3. Acute ischemic stroke symptoms within 4.5 hours of last known well time.
4. Baseline National Institutes of Health Stroke Scale (NIHSS) score ≥4.
5. Poor neurological improvement 1 hour after intravenous thrombolysis, defined as NIHSS decrease \<2 points, or neurological worsening within 1 hour, defined as NIHSS increase ≥1 point.
6. Not planned for or not eligible for endovascular treatment.
7. Subject or legally authorized representative can provide written informed consent.

Exclusion Criteria:

1. Evidence of intracranial hemorrhage on imaging before randomization.
2. Non-ischemic intracranial pathologies, such as vascular malformation, aneurysm, tumor, abscess, or demyelinating disease.
3. Large or medium vessel stenosis requiring thrombectomy or intra-arterial thrombolysis.
4. Contraindications to tirofiban, including but not limited to:Known hypersensitivity to tirofiban; Severe hepatic dysfunction (ALT \>2× ULN or AST \>2× ULN); Severe renal dysfunction (serum creatinine \>1.5× ULN); Advanced heart failure (NYHA class III-IV); Coagulation disorders or history of systemic bleeding; History of thrombocytopenia or neutropenia; Prior drug-induced hematologic disease or liver dysfunction; Leukopenia (\<2×10\^9/L) or platelet count \<100×10\^9/L.
5. Use of tirofiban or other GP IIb/IIIa inhibitors before randomization, or planned use of such agents after randomization.
6. Definite cardioembolic source, including but not limited to: chronic or paroxysmal atrial fibrillation, sick sinus syndrome, mitral stenosis, mechanical prosthetic heart valves, infective endocarditis, history of intracardiac thrombus, myocardial infarction within 3 months, dilated cardiomyopathy, spontaneous left atrial echo contrast, or left ventricular ejection fraction \<30%.
7. Pregnancy or lactation.
8. Expected survival \<6 months.
9. Pre-existing neurological or psychiatric disorders that may interfere with outcome assessment.
10. Unlikely to complete 90-day follow-up.

Where this trial is running

Beijing, Beijing Municipality

• Beijing Anzhen Hospital,Capital Medical University — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Xiaochuan Huo

Conditions Acute Ischemic Stroke; stroke; tirofiban; thrombolysis