Teneteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-Ⅳ (TRACE Ⅳ)

Capital Medical University

Status and phase: Enrolling; Phase 3

Conditions: Minor Ischemic Stroke

Treatments: Drug: Control group (Aspirin combined with clopidogrel); Drug: rhTNK-tPA

Study type: Interventional

Funder types: Other

Identifiers

NCT06414499

NCRC-2024-03

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,386 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,386 participants in 2 patient groups, including a placebo group

Aspirin combined with clopidogrel

Placebo Comparator group

Description:

Aspirin 100mg combined with clopidogrel 300mg, plus placebo intravenous rhTNK-tPA

Treatment:

Drug: Control group (Aspirin combined with clopidogrel)

rhTNK-tPA (0.25 mg/kg)

Experimental group

Description:

rhTNK-tPA (0.25 mg/kg, max 25 mg) with placebo oral aspirin and clopidogrel

Treatment:

Drug: rhTNK-tPA