Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-Ⅱ

Study Overview
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Brief Summary
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A Phase Ⅲ, Multicenter, Prospective, Randomized, Open Label, Blinded-endpoint (PROBE) Controlled Trial of Recombinant Human TNK Tissue-type Plasminogen Activator (rhTNK-tPA) for Injection Versus Alteplase for Acute Ischemic Stroke Within 4.5 Hours

Detailed Description
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To test the hypothesis that rhTNK-tPA is non-inferior to alteplase in thrombolysis treatment when administered within 4.5 hours of ischemic stroke onset.

Official Title
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A Phase 3, Multicentre,Open-label, Randomised Controlled, Non-inferiority Trial

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Drug: rt-PA
* Drug: rhTNK-tPA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years old, no gender limitation; The time from onset to treatment was < 4.5h;The time at which symptoms begin is defined as the time at which they finally appear normal; The clinical diagnosis was ischemic stroke (the diagnosis followed the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018); MRS before onset was 0-1 points Baseline NIHSS 5-25(both included); Informed consent from the patient or surrogate. Exclusion Criteria: Intended to proceed endovascular treatment; NIHSS consciousness score >2; Allergy to tenecteplase or alteplase; Past history of intracranial hemorrhage ; A history of severe head trauma or stroke within 3 months; A history of intracranial or spinal surgery within 3 months; A history of gastrointestinal or urinary bleeding within 3 weeks; 2 weeks of major surgery; Arterial puncture was performed at the hemostasis site that was not easily compressed within 1 week; Intracranial tumors (except neuroectodermal tumors, such as meningiomas), large intracranial aneurysms; Intracranial hemorrhage (including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/extradural hematoma, etc.); Active visceral bleeding; Aortic arch dissection was found; After active antihypertensive treatment, hypertension is still not under control: systolic blood pressure ≥180 mm Hg, or diastolic blood pressure ≥100 mm Hg; Propensity for acute bleeding, including platelet counts of less than 100×109/ L or otherwise; Blood glucose <2.8 mmol/L or >22.22 mmol/L; Oral warfarin anticoagulant with INR>1.7 or PT>15 s; Heparin treatment was received within 24 h; Thrombin inhibitors or factor Xa inhibitors were used within 48 h; Head CT or MRI showed a large infarction (infarcted area > 1/3 of the middle cerebral artery); Subjects who are unable or unwilling to cooperate due to hemiplegia (Todd's palsy) after epileptic seizure or other neurological/psychiatric disorders; Pregnant women, lactating women, or subjects who do not agree to use effective contraception during the trial; Participation in other clinical trials within 3 months prior to screening; Unsuitability or participation in this study as judged by the Investigator may result in subjects being exposed to greater risk.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: multicenter, prospective, randomized, open label, blinded-endpoint (PROBE)，Parallel controls，Non-inferiority
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: rhTNK-tPA (0.25mg/kg)<br>rhTNK-tPA (0.25mg/kg) is given as a single, intravenous bolus (within 5-10 seconds) immediately upon randomization. Maximum dose 25mg. | Drug: rhTNK-tPA<br>* Subjects will be randomized to rhTNK-tPA or rt-PA in a 1:1 ratio.<br>* Other names: Recombinant Human TNK Tissue-type Plasminogen Activator for Injection;|
| Active Comparator: rt-PA (0.9mg/kg)<br>10% dose of rt-PA (0.9 mg/kg) is given as bolus and the remainder in 1 hour. Maximum dose 90mg. | Drug: rt-PA<br>* Subjects will be randomized to rhTNK-tPA or rt-PA in a 1:1 ratio.<br>* Other names: Alteplase injection (rt-PA);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Excellent functional outcome | Proportion of subjects with mRS(0-1) at 90 days. | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Good functional outcome | Proportion of subjects with mRS(0-2) at 90 days. | 90 days | 
| National Institutes of Health Stroke Scale (NIHSS) | Proportion of subjects with NIHSS score ≥ 4 improved compared with baseline at 24 or with NIHSS 0-1 at 24 hours and 7 days. | 24 hours，day7 | 
| EQ-5D | Quality of life measured by EQ-5D scale. | 90 days | 
| Barthel (BI) | Global function of daily living defined as BI ≥ 95 at 90 days. | 90 days | 
| Modified Rankin Scale(mRS) | Ordinal distribution of mRS at 90 days. | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rhTNK-tPA, acute, stroke, phaseⅢ, Acute Ischemic Stroke, rt-PA