Clinical trial NCT06414499: Teneteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-Ⅳ(TRACE Ⅳ)
Official title: TNK-tPA Treatment for Acute Minor Ischemic Stroke：A Multicenter, Prospective，Randomized，Open Label, Blinded-endpoint Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Tenecteplase
Minor Ischemic Stroke
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2024-05-16
Enrollment: 1394
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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 12 hours of symptoms onset (symptom onset is defined by the "last seen normal" principle for wake-up stroke) accompanied with measurable neurological deficit and DWI/FLAIR mismatch 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 according to the guideline. The primary endpoint is excellent functional outcome (Modified Rankin Scale score, mRS 0-1) at 90-day.

Eligibility criteria: Inclusion Criteria

1. Age ≥ 18 years;
2. Can be treated with study drug within 12 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. DWI/FLAIR mismatch on magnetic resonance imaging.
5. Pre-stroke mRS 0-1;
6. Informed consent signed.

Exclusion Criteria

1. Contradictory or unable to complete MRI examination.
2. Planned or likely acute endovascular treatments (any angioplasty or vascular surgery);
3. NIHSS 1a \> 2;
4. Known allergic to rhTNK-tPA;
5. Known history of intracranial hemorrhage;
6. Clinical stroke or serious head/spinal trauma within 3 months;
7. Intracranial or spinal surgery within 3 months;
8. Known history of gastrointestinal or urinary tract hemorrhage in the previous 21 days.
9. Participants with a history of major surgery in the previous 14 days;
10. Arterial puncture at a non-compressible site in the previous 7 days.
11. Participants with intracranial tumors (excluding neuroectoderm origin, such as meningioma), huge intracranial aneurysm, or arterio-venous malformation.
12. Intracranial hemorrhage (including cerebral parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/epidural hematoma)
13. Participants with active visceral bleeding;
14. Participants with aortic arch dissection;
15. Participants with a known bleeding diathesis or with a platelet count \< 100×109/L;
16. Participants with a systolic blood pressure \> 180 or a diastolic blood pressure \> 100 mmHg after repeated measurements and aggressive treatments;
17. Blood glucose \< 2.8 or \> 22.2 mmol / L);
18. Clear indication for anticoagulation (presumed cardiac source of embolus, e.g., atrial fibrillation, prosthetic cardiac valves known or suspected endocarditis);
19. Receive intravenous thrombolysis within 24 hours;
20. Receive direct oral anticoagulant therapy with international normalized ratio (INR) \> 1.7s or PT \> 15 s;
21. Receive low molecular weight heparin or heparinoid within 24 hours;
22. Receive thrombin inhibitors or factor Xa inhibitors within 48 hours;
23. Receive GP2b3a inhibitors within 72 hours;
24. Participants who have large areas (greater than one third of middle cerebral artery territory) of obvious low density on the baseline CT scan;
25. Participants with a seizure at onset thought to be presenting with postictal paralysis (Todd's paralysis) mimicking stroke.
26. Participants with severe infection, such as bacterial endocarditis, pericarditis, acute pancreatitis;
27. Pregnant, currently trying to become pregnant, or of child-bearing potential and not using birth control;
28. Participation in another clinical study with an experimental product in the previous 3 months;
29. Participants deemed unsuitable for participation in this trial by the investigator or those for whom participation in this trial may result in greater risks.

Primary outcomes:
measure: Excellent functional outcome (Modified Rankin Scale score, mRS 0-1) at 90-day (± 7 days).
timeFrame: at 90-day (± 7 days)
Secondary outcomes:
measure: Good functional outcome (mRS 0-2) at 90-day (± 7 days)
timeFrame: at 90-day (± 7 days)
measure: Ordinal distribution of mRS scores at 90-day (± 7 days)
timeFrame: at 90-day (± 7 days)
measure: NIHSS 0-1 at 24-hour, 7-day or discharge (analyze which occurs first) or/ neurological improvement (NIHSS decreased≥2 from baseline)
timeFrame: at 24-hour, 7-day or discharge (analyze which occurs first)
measure: New clinical vascular events (ischemic stroke/ hemorrhagic stroke/ myocardial infarction/vascular death) at 90-day (± 7 days), with each vascular event being independently evaluated.
timeFrame: at 90-day (± 7 days)
measure: Symptomatic intracranial hemorrhage according to the ECASSIII criteria at 36-hour, 7-day or discharge (analyze which occurs first).
timeFrame: at 36-hour, 7-day or discharge (analyze which occurs first)
measure: Symptomatic intracranial hemorrhage according to the ECASSIII criteria at 90-day (± 7 days)
timeFrame: at 90-day (± 7 days)
measure: PH2 type intracranial hemorrhage according to the SITS criteria at 90-day (± 7 days)
timeFrame: at 90-day (± 7 days)
measure: Any intracranial hemorrhage at 90-day (± 7 days)
timeFrame: at 90-day (± 7 days)
measure: Moderate and severe bleeding events according to the GUSTO criteria at 90-day (± 7 days)
timeFrame: at 90-day (± 7 days)
measure: Total mortality at 90-day (± 7 days)
timeFrame: at 90-day (± 7 days)
measure: Adverse events/Severe adverse events reported by investigators at 90-day (± 7 days)
timeFrame: at 90-day (± 7 days)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital
state: Beijing
Study officials:
affiliation: Beijing Tiantan Hospital
name: Yongjun Wang, MD, PhD
role: STUDY_DIRECTOR
References: