Clinical trial NCT05752916: Intravenous Thrombolysis With rhTNK-tPA for Acute Non-large Vessel Occlusion in Extended Time Window
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Acute Ischemic Stroke
Keywords: acute ischemic stroke
extended time window
non-large vessel occlusion
intravenous thrombolysis
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
Collaborators: name: Guangzhou Recomgen Biotech Co., Ltd.
name: Beijing Hospitals Authority
First posted: 2023-03-03
Enrollment: 568
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: prospective, randomized, open label, blinded-endpoint (PROBE)
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 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

Primary outcomes:
measure: Excellent functional outcome
timeFrame: 90±7 days
Secondary outcomes:
measure: modified Rankin Scale (mRS) score
timeFrame: 90±7 days
measure: Good functional outcome
timeFrame: 90±7 days
measure: Rate of successful reperfusion
timeFrame: 24 hours (-2/+12 hours)
measure: Infarct volume at 24 hours (-2/+12 hours)
timeFrame: 24 hours (-2/+12 hours)
measure: Early clinical recovery
timeFrame: 24 hours (-2/+12 hours)
measure: Change of National Institutes of Health Stroke Scale (NIHSS)
timeFrame: 7±2 days
measure: Functional health status and quality of life
timeFrame: 90±7 days
Other outcomes:
measure: Incidence of clinically significant intracranial hemorrhage
timeFrame: 36 hours
measure: Incidence of major bleeding
timeFrame: 90±7 days
measure: All-cause mortality
timeFrame: 90±7 days
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Junwei Hao, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Xuanwu Hospital, Beijing
name: Qingfeng Ma, MD
role: PRINCIPAL_INVESTIGATOR
References: