Acute Ischemic Stroke
Conditions
Keywords
acute ischemic stroke, extended time window, non-large vessel occlusion, intravenous thrombolysis
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.
Interventions
DRUGrhTNK-tPA
Recombinant human TNK tissue-type plasminogen activator. Patients will receive intravenous rhTNK-tPA (0.25mg/kg, maximum 25mg, administered as a bolus over 5-10 seconds).
Aspirin (150-300mg) is offered to patients allocated in the control arm, unless contraindicated. According to Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke 2023, 150-300mg aspirin alone is recommended for acute stroke treatment in patients who are otherwise eligible for intravenous thrombolysis or EVT as soon as possible (Class 1 of recommendation, Level A of evidence). The aspirin dose can be changed to 50-300 mg/day after the acute phase. Clopidogrel is indicated as an alternative in case of aspirin intolerance (Class 2 of recommendation, Level C of evidence)
Sponsors
CSPC Mingfule Pharmaceutical (Guangzhou) Co., Ltd.
Beijing Hospitals Authority
Xuanwu Hospital, Beijing
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
An imaging core laboratory (ICL) is to provide an unbiased assessment of imaging measures. They are knowledgeable in the analysis of neuroradiological images and will be blinded, i.e. unaware of the patient's treatment allocation and trial outcome.
Intervention model description
prospective, randomized, open label, blinded-endpoint (PROBE)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Excellent functional outcome | 90±7 days | Proportion of subjects with mRS 0-1 at 90±7 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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 |
| 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 |
| 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) |
Other
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality | 90±7 days | All-cause mortality at 90±7 days |
| Incidence of clinically significant intracranial hemorrhage | 36 hours | Incidence of sICH (Heidelberg criteria) measured at 36 hours |
| Incidence of major bleeding | 90±7 days | Incidence of major bleeding defined as GUSTO severe/life threatening or moderate bleeds measured at 90±7 days |
Countries
China
Outcome results
None listed