Intravenous Thrombolysis With Recombinant Human TNK Tissue-type Plasminogen Activator (rhTNK-tPA) for Acute Non-large Vessel Occlusion in Extended Time Window--A Multicenter, Prospective, Randomized, Open-label, Blinded End-point Trial

[2022]205

This study is designed to evaluate the efficacy of IV rhTNK-tPA between 4.5 to 24 hours from symptom onset in patients presenting with a non-large vessel occlusion ischemic stroke.

2023-06-02

2024-06-30

2024-12-30

Recruiting

Early phase I

568

Inclusion Criteria: * The clinical diagnosis is acute ischemic stroke (the criteria followed the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018). * Age≥18 years * Pre-stroke mRS score≤1 points * Baseline NIHSS 4-25 (both included) at the time of randomization * Onset (last-seen-well) time to treatment time between 4.5 and 24 hours * Informed consent from the patient or surrogate * The presence of a Target Mismatch on CT perfusion: ischemic core volume\<50ml (defined as rCBF\<30%), mismatch ratio≥1.2 (Tmax\>6 sec lesion/core volume lesion), mismatch volume≥10ml Exclusion Criteria: * Treated with intravenous thrombolysis within 72 hours * Have a clear contraindication for intravenous thrombolysis * Intended to proceed endovascular treatment * Rapidly improving symptoms, particularly if in the judgment of the managing clinician that the improvement is likely to result in a NIHSS score\<4 at randomization * Woman of childbearing potential who is known to be pregnant or who has a positive pregnancy test on admission * Brain tumor (with mass effect) * Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency * Coagulation Disorders caused by diseases or anticoagulants: warfarin was used with International Normalized Ratio (INR)\>1.7 or PT\>15s; heparin was administered within 24 hours; novel oral anticoagulants were used within 48 hours * Glycoprotein IIb-IIIa inhibitors were used within the past 72 hours * Baseline platelet count \<100×109/L * Known severe renal insufficiency with eGFR\<30ml/min or serum creatinine\>2.5mg/dl * Undergoing hemodialysis or peritoneal dialysis; known severe intolerance to contrast media * Suspected aortic dissection * Parenchymal organ surgery or biopsy within the previous 1 month * Any active bleeding within the previous 1 month (including gastrointestinal or urinary bleeding) * Known severe allergy (more than a rash) to contrast media uncontrolled by medications * Refractory hypertension (defined as persistent systolic blood pressure\>185mmHg or diastolic blood pressure\>110mmHg) * Expected survival time\<0.5 year (such as complicated with malignant tumor, serious heart and lung diseases, etc.) * Participants in other interventional randomized trials that may confound the outcome assessment * Other circumstances that the investigator considers inappropriate for participation in the trial or that may pose significant risks to patients (e.g., inability to understand and/or follow the study procedures and/or follow up due to mental disorders, cognitive or emotional disorders) Specific Neuroimaging Exclusion Criteria: * Evidence of acute intracranial hemorrhage * Presence of proximal arterial occlusion on CTA/MRA (e.g., intracranial ICA, MCA-M1 and dominant M2 segments, and vertebrobasilar arteries) * Ischemic core volume\>1/3 of the MCA territory defined on CT/MRI

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2023-08-14