Overview
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.
Description
OPTION is a multicenter, prospective, randomized, open label, blinded-endpoint (PROBE) controlled trial of thrombolysis with rhTNK-tPA versus standard of care. A total of 568 patients will be enrolled at approximately 40 centers around China.
Eligibility
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