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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Minor Ischemic Stroke
• Intervention / Treatment: Drug: Control group (Aspirin combined with clopidogrel); Drug: rhTNK-tPA

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.

• Study Type: Interventional
• Enrollment (Estimated): 1386
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yongjun Wang, MD, PhD; Phone Number: 86-13911172565; Email: yongjunwang@ncrcnd.org.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Beijing Tiantan Hospital
      • Contact: Yongjun Wang, Dr.; Email: yongjunwang111@aliyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Aspirin combined with clopidogrel; Aspirin 100mg combined with clopidogrel 300mg, plus placebo intravenous rhTNK-tPA	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.
Experimental: rhTNK-tPA (0.25 mg/kg); rhTNK-tPA (0.25 mg/kg, max 25 mg) with placebo oral aspirin and clopidogrel	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 and clopidogrel 300 mg are administered within 6 ± 2 hours following thrombolytic therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Excellent functional outcome (Modified Rankin Scale score, mRS 0-1) at 90-day (± 7 days).	Modified Rankin Scale score, mRS 0-1	at 90-day (± 7 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Good functional outcome (mRS 0-2) at 90-day (± 7 days)		at 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.		at 90-day (± 7 days)
mRS score at 90-day (± 7 days)	shift analysis/ordinal distribution of mRS score at 90-day (±7 days)	at 90-day (± 7 days)
COSMOS Scale 0-1 at 90-day (±7days)		90-day± 7days
COSMOS scale at 90-day (±7 days)	shift analysis/ordinal distribution of COSMOS scale at 90-day (±7 days)	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)		at 24-hour, 7-day or before discharge (analyze which occurs first)
Neurological deterioration at 90 days	defined as an increase of ≥4 points in NIHSS score compared to baseline.	90-day (±7 days)
European quality of life visual analogue scale at 90 days		at 90-day (± 7 days)
Symptomatic intracranial hemorrhage according to the ECASSIII criteria within 36-hour.		within 36-hour
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)

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Study Director: Yongjun Wang, MD, PhD, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2025
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: May 10, 2024
• First Submitted That Met QC Criteria: May 10, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): July 24, 2025
• Last Update Submitted That Met QC Criteria: July 20, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: minor stroke; tenecteplase
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Ischemic Stroke; Stroke; Ischemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrin Modulating Agents; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Neurotransmitter Agents; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel; Aspirin
• Other Study ID Numbers: NCRC-2024-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No