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

Official title

Safety and Efficacy of Early Administration of Tirofiban in Patients Treated With Tenecteplase for Acute Ischemic Stroke

Overview

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.

Detailed 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.

Interventions

• Drug Tirofiban Hydrochloride
  Patients will receive a continuous intravenous infusion of tirofiban 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 after start of tenecteplase treatment within 4-24 hours. 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
• Drug Placebo
  Patients will receive a continuous intravenous infusion of placebo 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 after start of tenecteplase treatment within 4-24 hours. 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 randomiz

Primary outcome measures

• Excellent functional outcome [Time frame: 90 days post-randomization]

Secondary outcome measures (10)

• Ordinal degree of disability [Time frame: 90 days post-randomization]
• Functionally independent [Time frame: 90 days post-randomization]
• Ambulatory or bodily needs capable or better [Time frame: 90 days post-randomization]
• Early neurologic improvement [Time frame: 48 hours post-randomization]
• Health-related quality of life [Time frame: 90 days post-randomization]
• Symptomatic intracranial hemorrhage [Time frame: 48 hours post-randomization]
• Radiologic intracranial hemorrhage rate [Time frame: 48 hours post-randomization]
• Mortality [Time frame: 90 days post-randomization]
• Incidence of non-hemorrhagic serious adverse events [Time frame: Within 90 days post-randomization]
• Other serious adverse events [Time frame: Within 90 days post-randomization]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years old;
• 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);
• NIHSS ≥ 4 points before randomization;
• The patient or their family members sign a written informed consent form.

Exclusion criteria

• Intracranial hemorrhage was confirmed by CT or MRI after intravenous thrombolysis and before randomization;
• 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;
• 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;
• Blood platelet count was lower than 100×10\^9/L;
• Renal insufficiency, glomerular filtration rate < 30 mL/min;
• Pregnant or lactating women;
• Allergic to tirofiban, nickel, titanium or their alloys;
• Prior neurological or psychiatric illness that prevents assessment of neurological function;
• Pre-existing bleeding disease, severe heart, liver, or kidney disease, or sepsis;
• Brain tumors with a space-occupying effect on imaging (other than micromeningiomas);
• Intracranial aneurysm, arteriovenous malformation;
• Life expectancy of any advanced disease < 6 months;
• Participating in other clinical trials.

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 · 38 centers

• Mingguang People's Hospital — Chuzhou
• Longyan People´s Hospital, Longyan City — Longyan
• The Second Affiliated Hospital of Guangxi Medical University — Nanning
• Huangmei People's Hospital — Huanggang
• Yiling People's Hospital of Yichang city — Yichang
• Hunan Xupu Chengnan Hospital — Huaihua
• People's Hospital Of Shaodong — Shaoyang
• Shaoshan People's Hospital — Xiangtan
• … and 30 more centers

Publications

• INSTANT Trial Authors for the INSTANT Investigators; Liu X, Zhang F, Zhang C, Li Z, Yuan G, Kong D, Xie S, Zhou M, Ye J, Lai Z, Li D, Xu H, Chen L, Cheng F, Shi Y, Chen B, Hu W, Liu H, Yin Y, Deng X, Xie Z, Li C, Shi J, Mei D, Liu B, Wang B, Zhou R, Liu J, Shen L, Hu H, Xiao G, Guan X, Yuan S, Lv X, Liang S, Zeng X, Chen Y, Cao W, Zheng C, Liu Y, Li J, Guan B, Lai T, Sun W, Zeng H, Zhang J, Li S, PMID 42100960

Identifiers

NCT: NCT05604638 · SecondAHGuangxiMU

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗