Early Administration of Tirofiban in Patients Treated With Tenecteplase for Acute Ischemic Stroke (INSTANT)

Second Affiliated Hospital of Guangxi Medical University

Status and phase: Enrolling; Phase 3

Conditions: Acute Ischemic Stroke

Treatments: Drug: Placebo; Drug: Tirofiban Hydrochloride

Study type: Interventional

Funder types: Other

Identifiers

NCT05604638

SecondAHGuangxiMU

Details and patient eligibility

About

The purpose of this study is to assess the safety and efficacy of early administration of tirofiban in patients treated with tenecteplase for acute ischemic stroke.

Full description

Intravenous thrombolysis with alteplase is recommended in treatment guidelines for patients with acute ischemic stroke. Previous studies showed that intravenous tenecteplase (0.25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischemic stroke who meet standard criteria for thrombolysis. After thrombolysis-induced recanalisation, reocclusion occurs in 14-34% of patients, probably because of platelet activation. Early administration of antiplatelet therapy after intravenous thrombolysis could reduce the risk of reocclusion and improve outcome. The purpose of this study is to assess the safety and efficacy of early administration of tirofiban in patients treated with tenecteplase for acute ischemic stroke.

Enrollment: 348 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 18 years old;
2. Within 4-24 hours after intravenous thrombolytic therapy with tenerplase for acute ischemic stroke, there was no significant change in symptoms compared to the baseline (defined as an increase or decrease of 0 or 1 point in the NIHSS score), and neurological function deteriorated (defined as an increase of ≥ 2 in the NIHSS score compared to the baseline) Fluctuations in neurological function (defined as an increase of 4 points or more in the NIHSS score compared to the baseline and then a decrease of 4 points or more);
3. NIHSS ≥ 4 points before randomization;
4. The patient or their family members sign a written informed consent form.

Exclusion criteria

1. Intracranial hemorrhage was confirmed by CT or MRI after intravenous thrombolysis and before randomization;
2. CTA/MRA/DSA showed occlusion of the internal carotid artery, middle cerebral artery M1, M2 or M3 segment, anterior cerebral artery A1, A2 or A3 segment, posterior cerebral artery P1, P2 or P3, vertebral or basilar artery;
3. Confirmed or suspected cardioembolic stroke mechanisms, including any of the following: documented cardiac sources of thromboembolism: chronic or paroxysmal atrial fibrillation, rheumatic mitral stenosis, prosthetic heart valves, infective endocarditis, intracardiac thrombus or implanted prosthetic material, dilated cardiomyopathy (left ventricular ejection fraction <40%), or spontaneous echo contrast in the left atrium; other laboratory-confirmed embolic sources: patent foramen ovale with concomitant atrial septal aneurysm, or cryptogenic stroke with a CHADS-VASC score ≥ 2 indicating high thromboembolic risk;
4. Blood platelet count was lower than 100×10^9/L;
5. Renal insufficiency, glomerular filtration rate < 30 mL/min;
6. Pregnant or lactating women;
7. Allergic to tirofiban, nickel, titanium or their alloys;
8. Prior neurological or psychiatric illness that prevents assessment of neurological function;
9. Pre-existing bleeding disease, severe heart, liver, or kidney disease, or sepsis;
10. Brain tumors with a space-occupying effect on imaging (other than micromeningiomas);
11. Intracranial aneurysm, arteriovenous malformation;
12. Life expectancy of any advanced disease < 6 months;
13. Participating in other clinical trials.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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348 participants in 2 patient groups, including a placebo group

Tirofiban

Experimental group

Description:

Patients are treated with intravenous tenecteplase first, and patients who meet the selection criteria will be randomly assigned to either the tirofiban or placebo group in a 1:1 ratio. Patients assigned to the tirofiban group will be treated with intravenous tirofiban. It is recommended to start treatment as soon as possible (within 10 minutes recommended) after randomization. Tirofiban will be administered at a dose of 0.3 μg per kilogram of body weight per minute for 30 minutes, followed by a continuous infusion of 0.075 μg per kilogram per minute for 47.5h. Aspirin placebo (1 tablet) and/or clopidogrel placebo (1 tablet) will be given orally at 24h after intravenous tenecteplase. Antiplatelet therapy with aspirin (100 mg) and/or clopidogrel (75 mg) will be administered at 44h after randomization until the follow-up period of 90 days.

Treatment:

Drug: Tirofiban Hydrochloride

Placebo

Placebo Comparator group

Description:

All patients are treated with intravenous tenecteplase first, and patients who meet the selection criteria will be randomly assigned to either the tirofiban or placebo group in a 1:1 ratio. Patients assigned to the placebo group will be treated with intravenous saline. It is recommended to start treatment as soon as possible (within 10 minutes recommended) after randomization. Placebo will be administered at a dose of 0.3 μg per kilogram of body weight per minute for 30 minutes, followed by a continuous infusion of 0.075 μg per kilogram per minute for 47.5h. Aspirin (1 tablet) and/or clopidogrel (1 tablet) will be given orally at 24h after intravenous tenecteplase. Antiplatelet therapy with aspirin (100 mg) and/or clopidogrel (75 mg) will be administered at 44h after randomization until the follow-up period of 90 days.

Treatment:

Drug: Placebo