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

TNK-tPA Treatment for Acute Minor Ischemic Stroke：A Multicenter, Prospective, Open Label, Blinded-endpoint, Randomized Controlled Trial

The trial is a multicenter, prospective, open-label, blinded-endpoint randomized controlled design. Participants with acute minor ischemic stroke (baseline NIHSS≤5) accompanied with measurable neurological deficit will be randomized 1:1 to 0.25mg/kg intravenous tenecteplase or standard medical treatment.

Study Overview

• Status: Recruiting
• Conditions: Minor Ischemic Stroke; Tenecteplase
• Intervention / Treatment: Drug: rhTNK-tPA; Drug: Single/dual antiplatelet therapy

Detailed Description

The study will be a multicenter, prospective, open-label, blinded-endpoint randomized controlled trial (2 arms with 1:1 randomization). 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) accompanied with measurable neurological deficit will be enrolled. The measurable neurological deficit is defined as impairment of 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. Control group (standard medical care): Single/dual antiplatelet therapy (aspirin, clopidogrel, ticagrelor, etc.) according to the guideline. The primary endpoint is excellent functional outcome (Modified Rankin Scale score, mRS 0-1) at 90-day.

• Study Type: Interventional
• Enrollment (Estimated): 1874
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yongjun Wang, MD, PhD; Phone Number: 86-13911172565; Email: yongjunwang@ncrcnd.org.cn
• Study Contact Backup: Name: Jing Jing, MD, PhD; Phone Number: 86-15810312511; Email: jingj_bjttyy@163.com

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. Can be treated with study drug within 4.5 hours of symptoms onset*(*Symptom onset is defined by the "last seen normal" principle);
3. Clinical diagnosis of minor ischemic stroke (baseline NIHSS≤5) with a measurable neurological deficit defined as impairment of language or motor function;
4. Pre-stroke mRS 0-1;
5. Informed consent signed.

Exclusion Criteria

1. Planned or likely to receive acute endovascular treatments (any angioplasty or vascular surgery);
2. NIHSS 1a > 2;
3. Known allergic to rhTNK-tPA;
4. Known history of intracranial hemorrhage;
5. Clinical stroke or serious head/spinal trauma within 3 months;
6. Intracranial or spinal surgery within 3 months;
7. Known history of gastrointestinal or urinary tract hemorrhage in the previous 21 days.
8. Participants with a history of major surgery in the previous 14 days;
9. Arterial puncture at a non-compressible site in the previous 7 days.
10. Participants with intracranial tumors (excluding neuroectoderm origin, such as meningioma), huge intracranial aneurysm, or arterio-venous malformation.
11. Intracranial hemorrhage (including cerebral parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/epidural hematoma)
12. Participants with active visceral bleeding;
13. Participants with aortic arch dissection;
14. Participants with a known bleeding diathesis or with a platelet count < 100×10^9/L;
15. Participants with a systolic blood pressure ≥ 180 or a diastolic blood pressure ≥ 100 mmHg after repeated measurements and aggressive treatments;
16. Blood glucose <50 or > 400 mg/dl (< 2.8 or > 22.2 mmol / l);
17. Clear indication for anticoagulation (presumed cardiac source of embolus, e.g., atrial fibrillation, prosthetic cardiac valves known or suspected endocarditis);
18. Receive intravenous thrombolysis within 24 hours;
19. Receive direct oral anticoagulant therapy with international normalized ratio (INR) > 1.7s or PT > 15 s;
20. Receive low molecular weight heparin or heparinoid within 24 hours;
21. Receive thrombin inhibitors or factor Xa inhibitors within 48 hours;
22. Receive GP2b3a inhibitors within 72 hours;
23. Participants who have large areas (greater than one third of middle cerebral artery territory) of obvious low density on the baseline CT scan;
24. Participants with a seizure at onset thought to be presenting with postictal paralysis (Todd's paralysis) mimicking stroke.
25. Participants with severe infection, such as bacterial endocarditis, pericarditis, acute pancreatitis;
26. Pregnant, currently trying to become pregnant, or of child-bearing potential and not using birth control;
27. Participation in another clinical study with an experimental product in the previous 3 months;
28. Participants deemed unsuitable for participation in this trial by the investigator or those for whom participation in this trial may result in greater risks.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rhTNK-tPA; Within 4.5 hours of symptom onset: Intervention group (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.	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.
Placebo Comparator: Standard medical care; Within 4.5 hours of symptom onset: Control group (standard medical care): Single/dual antiplatelet therapy (aspirin, clopidogrel, ticagrelor, etc.) according to the guideline.	Drug: Single/dual antiplatelet therapy; Single/dual antiplatelet therapy (aspirin, clopidogrel, ticagrelor, etc.) according to the guideline.

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	Time Frame
Good functional outcome (mRS 0-2) at 90-day (± 7 days)	at 90-day (± 7 days)
Ordinal distribution of mRS scores at 90-day (± 7 days)	at 90-day (± 7 days)
NIHSS 0-1 at 24-hour, 7-day or discharge (analyze which occurs first) or/ neurological improvement (NIHSS decreased≥2 from baseline)	at 24-hour, 7-day or discharge (analyze which occurs first)
Neurological impairment (NIHSS increased≥4 from baseline) 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)
Symptomatic intracranial hemorrhage according to the ECASSIII criteria at 36-hour, 7-day or discharge (analyze which occurs first).	at 36-hour, 7-day or discharge (analyze which occurs first)
Symptomatic intracranial hemorrhage according to the ECASSIII criteria at 90-day (± 7 days)	at 90-day (± 7 days)
PH2 type intracranial hemorrhage according to the SITS criteria at 90-day (± 7 days)	at 90-day (± 7 days)
Any intracranial hemorrhage at 90-day (± 7 days)	at 90-day (± 7 days)
Moderate and severe bleeding events according to the GUSTO criteria at 90-day (± 7 days)	at 90-day (± 7 days)
Total mortality at 90-day (± 7 days)	at 90-day (± 7 days)
Adverse events/Severe adverse events reported by investigators at 90-day (± 7 days)	at 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 (Estimated): May 20, 2024
• Primary Completion (Estimated): July 31, 2025
• Study Completion (Estimated): December 31, 2025

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): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 10, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Ischemia
• 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