Intravenous Thrombolysis With rhTNK-tPA for Acute Non-large Vessel Occlusion in Extended Time Window
- Conditions
- Acute Ischemic Stroke
- Interventions
- Drug: Antiplatelet Agents
- Registration Number
- NCT05752916
- Lead Sponsor
- Xuanwu Hospital, Beijing
- Brief Summary
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.
- Detailed Description
OPTION is a multicenter, prospective, randomized, open-label, blinded end-point (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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 568
-
Clinical diagnosis of acute ischemic stroke
-
Age≥18 years
-
Pre-stroke mRS score≤1 points
-
Disabling stroke defined as follows:
- Baseline NIHSS score 6-25 at the time of randomization,
- Or NIHSS 4-5 with disabling deficit (e.g. hemianopia, aphasia, loss of hand function) as determined by the managing clinician
-
Onset (last-seen-well) time to treatment time between 4.5 and 24 hours
-
Written informed consent from patients or legally responsible representatives
-
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
- Treatment with a thrombolytic within the last 72 hours or intention to receive intravenous thrombolysis
- Contraindication to thrombolysis
- Planned or anticipated treatment with endovascular therapy
- 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
- Pregnancy or lactating; formal testing needed in women of childbearing potential
- Brain tumor (with mass effect)
- Hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency
- Impairment in coagulation due to comorbid disease or anticoagulant use. If on warfarin, international normalized ratio (INR) >1.7 or prothrombin time >15s; if use of any direct oral anticoagulant within the last 48 hours; if use of heparin/heparinoid within the last 24 hours
- Use of glycoprotein Ⅱb-Ⅲa inhibitors within the last 72 hours
- Baseline platelet count <100,000/μL
- Undergoing hemodialysis or peritoneal dialysis; known severe renal insufficiency with glomerular filtration rate <30ml/min or serum creatinine >220mmol/L (2.5mg/dl)
- Suspected aortic dissection
- Major surgery or biopsy within the last 1 month
- Any active bleeding within the previous 1 month (including gastrointestinal or urinary bleeding)
- Known severe, life-threatening allergy (more severe than skin rash) to contrast agents
- Severe, uncontrolled hypertension (systolic blood pressure >185mmHg or diastolic blood pressure >110mmHg)
- Any terminal illness such that the patient would not be expected to survive more than half a year
- Current participation in any investigational study that may confound outcome assessment of the study
- Any condition that, in the judgement of the investigator, is inappropriate for participation in the trial or could impose hazards to the patient (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
- Acute large vessel occlusion on magnetic resonance/ computed tomography angiography, including internal carotid artery (ICA), middle cerebral artery M1 segment (MCA-M1）, vertebral artery and basilar artery
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intravenous rhTNK-tPA rhTNK-tPA rhTNK-tPA(0.25mg/kg) given as a single, intravenous bolus immediately upon randomization. Experimental treatment will be administered as a single intravenous bolus over 5-10 seconds as per the standard manufacturers' instructions for use. Standard Medical Treatment Antiplatelet Agents Antiplatelet therapy (aspirin or clopidogrel alone) at the discretion of local investigators according to Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke 2023.
- Primary Outcome Measures
Name Time Method Excellent functional outcome 90±7 days Proportion of subjects with mRS 0-1 at 90±7 days
- Secondary Outcome Measures
Name Time Method modified Rankin Scale (mRS) score 90±7 days Ordinal distribution of mRS at 90±7 days; modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)
Good functional outcome 90±7 days Proportion of subjects with mRS 0-2 at 90±7 days
Rate of successful reperfusion 24 hours (-2/+12 hours) \>90% reduction of the Tmax\>6s lesion volumes between the baseline and early follow-up at 24 hours (-2/+12 hours)
Infarct volume at 24 hours (-2/+12 hours) 24 hours (-2/+12 hours) The infarct volume is determined on evaluated on NCCT at 24 hours (-2/+12 hours)
Early clinical recovery 24 hours (-2/+12 hours) Proportion of subjects with NIHSS score≥8 improved compared with baseline or with NIHSS 0-1 at 24 hours (-2/+12 hours)
Change of National Institutes of Health Stroke Scale (NIHSS) 7±2 days Change of NIHSS score from baseline to 7 days (±2days)
Functional health status and quality of life 90±7 days Functional health status and quality of life (EQ-5D-5L) at 90±7 days
Trial Locations
- Locations (1)
Xuanwu Hospital, Capital Medical University
🇨🇳Beijing, China