Intravenous Tirofiban After Delayed Thrombolysis in Stroke

Official title

Intravenous Tirofiban Versus Placebo After Delayed Thrombolysis (4.5-24h) in Acute Ischemic Stroke (PEARL-TIRO): A Multicenter, Double-Blind, Double-Dummy, Randomized Controlled Trial

Overview

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

• Drug Tirofiban
  Tirofiban is administered as a loading dose and continuous intravenous infusion as soon as possible after the randomization.
• Drug Placebo
  Matched placebo will be infused in a similar fashion.

Primary outcome measures

• The modified Rankin Scale score (mRS) 0-1 [Time frame: 90 (±14) days]

Secondary outcome measures (4)

• Distribution of modified Rankin Scale score at 90 days [Time frame: 90 (±14) days]
• The modified Rankin Scale score 0-2 [Time frame: 90 (±14) days]
• Early neurological improvement [Time frame: 48 (±12) hours]
• Quality of life (EQ-5D-5L) [Time frame: 90 (±14) days]

Eligibility criteria

Inclusion criteria

• Aged 18 years or older;
• Clinical diagnosed acute ischemic stroke (AIS) with last known well time of 4.5-24 hours;
• 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

• Intracranial or subarachnoid hemorrhage confirmed by cranial computed tomography (CT) or magnetic resonance imaging (MRI), or any intracranial hemorrhage history;
• 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;
• 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%;
• Pre-stroke modified Rankin scale (mRS)≥2;
• Renal insufficiency (glomerular filtration rate < 30 mL/min or serum creatinine > 220 μmol/L \[2.5 mg/dl\]);
• Pregnant or lactating women;
• NCCT, CTA source imaging, or MRI-DWI showing ASPECTS or PC-ASPECTS < 6;
• Allergy to tirofiban, other glycoprotein IIb/IIIa inhibitors, aspirin or clopidogrel;
• History of bleeding disorder, severe heart, liver or kidney disease, or sepsis;
• 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;
• CT or MR evidence of mass effect or intracranial tumor (except small meningioma);
• CT or MR angiography evidence of intracranial arteriovenous malformations or aneurysm;
• Severe allergy to contrast agents (non-mild rash allergy) or absolute contraindication to iodine contrast;
• Any terminal illness with life expectancy less than 6 months;
• Participating in other clinical trials;
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University — Guangzhou

Identifiers

NCT: NCT07111806 · PEARL-TIRO

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗