Teneteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-Ⅳ

Official title

TNK-tPA Treatment for Acute Minor Ischemic Stroke：A Randomized, Double-blind, Double-dummy Controlled Trial

Overview

The purpose of this study is to evaluate the efficacy and safety of intravenous tenecteplase (0.25 mg/kg) compared with standard therapy in patients with acute ischemic stroke presenting with mild symptoms-defined as a National Institutes of Health Stroke Scale (NIHSS) score ≤5 accompanied by persistent unilateral limb weakness or speech impairment within 4.5 hours of onset.

Detailed description

This study is a multicenter, prospective, randomized, double-blind, double-dummy controlled (2 arms with 1:1 randomization) trial. Participants with acute minor ischemic stroke (baseline NIHSS≤5) within 4.5 hours of symptoms onset (symptom onset is defined by the "last seen normal" principle for wake-up stroke) will be enrolled. Eligible patients must have neurological deficits involving at least language or motor function. Participants will be randomized into 2 groups: Intervention group (rhTNK-tPA): 0.25mg/kg, the maximum dose does not exceed 25mg, plus placebo oral aspirin and clopidogrel. Aspirin 100mg and clopidogrel 300mg will be given within 6 ± 2 hours after thrombolytic therapy. Control group: Dual antiplatelet therapy with aspirin 100mg and clopidogrel 300mg, plus placebo intravenous rhTNK-tPA. Placebo oral aspirin and clopidogrel will be given within 6 ± 2 hours following the placebo thrombolytic therapy.The primary endpoint is an excellent functional outcome (a modified Rankin Scale score of 0-1) at 90-day.

Interventions

• Drug rhTNK-tPA
  rhTNK-tPA 0.25mg/kg, the maximum dose does not exceed 25mg: 1 vial is dissolved in 3ml of sterile water for injection to prepare a medicinal solution with a concentration of 5.33mg/ml. Calculate the total amount of the drug according to the weight of participant, and the maximum dose shall not exceed 25 mg. It is administered as a single bolus intravenous injection, and the injection is completed within 5-10 seconds. Additionally, placebo oral aspirin and clopidogrel are given. Aspirin 100 mg an
• Drug Control group (Aspirin combined with clopidogrel)
  Dual antiplatelets with aspirin 100mg and clopidogrel 300mg, plus placebo intravenous rhTNK-tPA. Placebo oral aspirin and clopidogrel are administered within 6 ± 2 hours following intravenous placebo.

Primary outcome measures

• Excellent functional outcome (Modified Rankin Scale score, mRS 0-1) at 90-day (± 7 days). [Time frame: at 90-day (± 7 days)]

Secondary outcome measures (12)

• Good functional outcome (mRS 0-2) at 90-day (± 7 days) [Time frame: at 90-day (± 7 days)]
• mRS score at 90-day (± 7 days) [Time frame: at 90-day (± 7 days)]
• COSMOS Scale 0-1 at 90-day (±7days) [Time frame: 90-day± 7days]
• COSMOS scale at 90-day (±7 days) [Time frame: 90-day± 7days]
• NIHSS 0-1 at 24-hour, 7-day or before discharge (analyze which occurs first) or/ neurological improvement (NIHSS decreased≥4 from baseline) [Time frame: at 24-hour, 7-day or before discharge (analyze which occurs first)]
• Neurological deterioration at 90 days [Time frame: 90-day (±7 days)]
• New clinical vascular events (ischemic stroke/ hemorrhagic stroke/ myocardial infarction/vascular death) at 90-day (± 7 days), with each vascular event being independently evaluated. [Time frame: at 90-day (± 7 days)]
• European quality of life visual analogue scale at 90 days [Time frame: at 90-day (± 7 days)]
• Symptomatic intracranial hemorrhage according to the ECASSIII criteria within 36-hour. [Time frame: within 36-hour]
• Symptomatic intracranial hemorrhage according to the ECASSIII criteria within 7 days or before discharge. [Time frame: within 7 days or before discharge]
• Symptomatic intracranial hemorrhage according to the ECASSIII criteria within 90-day (± 7 days) [Time frame: within 90-day (± 7 days)]
• PH2 type intracranial hemorrhage according to the Heidelberg criteria within 90-day (± 7 days) [Time frame: within 90-day (± 7 days)]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years;
• Onset-to-treatment time < 4.5 h; onset time defined as "last known well" time;
• Clinical diagnosis of minor ischemic stroke (NIHSS ≤ 5) with persistent unilateral limb weakness or speech symptoms, defined as a score of ≥1 on either the language item or a single limb item of the NIHSS;
• Pre-stroke mRS 0-1;
• Informed consent signed.

Exclusion criteria

• Planned or likely acute endovascular treatments before randomization;
• NIHSS 1a > 2;
• Known allergic to rhTNK-tPA;
• History of intracranial hemorrhage;
• Severe head trauma or previous stroke within 3 months；
• Intracranial or spinal surgery within 3 months;
• Gastrointestinal or urinary tract hemorrhage within 3 weeks；
• Major surgery within 2 weeks;
• Arterial puncture at a non-compressible site within 1 week；
• Intracranial tumors (excluding neuroectodermal tumors, e.g., meningiomas), large intracranial aneurysms, or arteriovenous malformations；
• Intracranial hemorrhage, including intraparenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, and subdural/epidural hematoma;
• Active visceral bleeding;
• Concomitantaortic arch dissection;
• Acute bleeding tendency, including platelet count <100×10⁹/L or other clinically significant conditions;
• Uncontrolled hypertension after active antihypertensive treatment: systolic blood pressure >180 mm Hg or diastolic >100 mm Hg;
• Blood glucose < 2.8 or > 22.2 mmol / L;
• Prior anticoagulant therapy, such as oral warfarin, with an INR >1.7 or PT >15 seconds;
• Use of heparin within 24 hours;
• Use of thrombin inhibitors or factor Xa inhibitors within 48 hours;
• Large cerebral infarction on head CT or MRI (infarction area >1/3 of the middle cerebral artery territory);
• Todd's paralysis after a seizure or other neurological/psychiatric disorders affecting cooperation;
• Severe, uncontrolled infections (e.g., acute pericarditis, infective endocarditis, or acute pancreatitis);
• Pregnant or breastfeeding women, or women unwilling to use effective contraception during the study period;
• Participation in another clinical trial within 3 months prior to screening;
• Other severe illnesses with a life expectancy of less than six months;
• Deemed unsuitable for the study or at increased risk by the investigator's judgment.

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

• Beijing Tiantan Hospital — Beijing

Identifiers

NCT: NCT06414499 · NCRC-2024-03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗