Teneteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-Ⅳ

NCT ID: NCT06414499

Last Updated: 2025-07-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1386 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-09
• Study Completion Date: 2026-10-31

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.

Conditions

Minor Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Aspirin combined with clopidogrel

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

Group Type: PLACEBO_COMPARATOR

Control group (Aspirin combined with clopidogrel)

Intervention Type: DRUG

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.

rhTNK-tPA (0.25 mg/kg)

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

Group Type: EXPERIMENTAL

rhTNK-tPA

Intervention Type: DRUG

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.

Interventions

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 and clopidogrel 300 mg are administered within 6 ± 2 hours following thrombolytic therapy.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Tiantan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yongjun Wang

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yongjun Wang, MD, PhD

Role: STUDY_DIRECTOR

Beijing Tiantan Hospital

Locations

Beijing Tiantan Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yongjun Wang, MD, PhD

Role: CONTACT

yongjunwang@ncrcnd.org.cn

86-13911172565

Facility Contacts

Yongjun Wang, Dr.

Role: primary

yongjunwang111@aliyun.com

Other Identifiers

NCRC-2024-03

Identifier Type: -

Identifier Source: org_study_id