Minor Ischemic Stroke
Conditions
Keywords
minor stroke, tenecteplase
Brief summary
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
DRUGrhTNK-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 and clopidogrel 300 mg are administered within 6 ± 2 hours following thrombolytic therapy.
DRUGControl 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.
Sponsors
Beijing Tiantan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years; 2. Onset-to-treatment time \< 4.5 h; onset time defined as last known well time; 3. 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; 4. Pre-stroke mRS 0-1; 5. Informed consent signed.
Exclusion criteria
1. Planned or likely acute endovascular treatments before randomization; 2. NIHSS 1a \> 2; 3. Known allergic to rhTNK-tPA; 4. History of intracranial hemorrhage; 5. Severe head trauma or previous stroke within 3 months； 6. Intracranial or spinal surgery within 3 months; 7. Gastrointestinal or urinary tract hemorrhage within 3 weeks； 8. Major surgery within 2 weeks; 9. Arterial puncture at a non-compressible site within 1 week； 10. Intracranial tumors (excluding neuroectodermal tumors, e.g., meningiomas), large intracranial aneurysms, or arteriovenous malformations； 11. Intracranial hemorrhage, including intraparenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, and subdural/epidural hematoma; 12. Active visceral bleeding; 13. Concomitantaortic arch dissection; 14. Acute bleeding tendency, including platelet count \<100×10⁹/L or other clinically significant conditions; 15. Uncontrolled hypertension after active antihypertensive treatment: systolic blood pressure \>180 mm Hg or diastolic \>100 mm Hg; 16. Blood glucose \< 2.8 or \> 22.2 mmol / L; 17. Prior anticoagulant therapy, such as oral warfarin, with an INR \>1.7 or PT \>15 seconds; 18. Use of heparin within 24 hours; 19. Use of thrombin inhibitors or factor Xa inhibitors within 48 hours; 20. Large cerebral infarction on head CT or MRI (infarction area \>1/3 of the middle cerebral artery territory); 21. Todd's paralysis after a seizure or other neurological/psychiatric disorders affecting cooperation; 22. Severe, uncontrolled infections (e.g., acute pericarditis, infective endocarditis, or acute pancreatitis); 23. Pregnant or breastfeeding women, or women unwilling to use effective contraception during the study period; 24. Participation in another clinical trial within 3 months prior to screening; 25. Other severe illnesses with a life expectancy of less than six months; 26. Deemed unsuitable for the study or at increased risk by the investigator's judgment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Excellent functional outcome (Modified Rankin Scale score, mRS 0-1) at 90-day (± 7 days). | at 90-day (± 7 days) | Modified Rankin Scale score, mRS 0-1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| mRS score at 90-day (± 7 days) | at 90-day (± 7 days) | shift analysis/ordinal distribution of mRS score at 90-day (±7 days) |
| COSMOS Scale 0-1 at 90-day (±7days) | 90-day± 7days | — |
| COSMOS scale at 90-day (±7 days) | 90-day± 7days | shift analysis/ordinal distribution of COSMOS scale at 90-day (±7 days) |
| NIHSS 0-1 at 24-hour, 7-day or before discharge (analyze which occurs first) or/ neurological improvement (NIHSS decreased≥4 from baseline) | at 24-hour, 7-day or before discharge (analyze which occurs first) | — |
| Neurological deterioration at 90 days | 90-day (±7 days) | defined as an increase of ≥4 points in NIHSS score compared to baseline. |
| New clinical vascular events (ischemic stroke/ hemorrhagic stroke/ myocardial infarction/vascular death) at 90-day (± 7 days), with each vascular event being independently evaluated. | at 90-day (± 7 days) | — |
| European quality of life visual analogue scale at 90 days | at 90-day (± 7 days) | — |
| Good functional outcome (mRS 0-2) at 90-day (± 7 days) | at 90-day (± 7 days) | — |
| Symptomatic intracranial hemorrhage according to the ECASSIII criteria within 7 days or before discharge. | within 7 days or before discharge | — |
| Symptomatic intracranial hemorrhage according to the ECASSIII criteria within 90-day (± 7 days) | within 90-day (± 7 days) | — |
| PH2 type intracranial hemorrhage according to the Heidelberg criteria within 90-day (± 7 days) | within 90-day (± 7 days) | — |
| Any intracranial hemorrhage within 90-day (± 7 days) | within 90-day (± 7 days) | — |
| Severe bleeding events according to the GUSTO criteria within 90-day (± 7 days) | within 90-day (± 7 days) | — |
| Total mortality within 90-day (± 7 days) | within 90-day (± 7 days) | — |
| Adverse events/Severe adverse events within 90-day (± 7 days) | within 90-day (± 7 days) | — |
| Symptomatic intracranial hemorrhage according to the ECASSIII criteria within 36-hour. | within 36-hour | — |
Countries
China
Contacts
Primary ContactYongjun Wang, MD, PhD
Outcome results
None listed