Using rhTNK-tPA for treating acute ischemic stroke in a longer time frame

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

This study is testing if a new treatment called rhTNK-tPA can help people who have had an acute ischemic stroke caused by smaller blood vessel blockages when given 4.5 to 24 hours after their symptoms start.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 568 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Xuanwu Hospital, Beijing (Academic / other)
• Locations: 1 site (Beijing)
• Trial ID: NCT05752916 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of intravenous rhTNK-tPA in patients with acute ischemic stroke caused by non-large vessel occlusion, specifically within a treatment window of 4.5 to 24 hours after symptom onset. It is a multicenter, prospective, randomized, open-label trial comparing rhTNK-tPA to standard care, aiming to enroll 568 patients across approximately 40 centers in China. The study will assess outcomes using a blinded endpoint approach to ensure unbiased results.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a clinical diagnosis of acute ischemic stroke and specific NIHSS scores indicating a disabling stroke.

Not a fit: Patients who have received thrombolytic treatment within the last 72 hours or have contraindications to thrombolysis may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for patients experiencing acute ischemic strokes beyond the current treatment window.

How similar studies have performed: Other studies have explored thrombolysis in extended time windows, but this specific approach with rhTNK-tPA is relatively novel.

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

Where this trial is running

Beijing

• Xuanwu Hospital, Capital Medical University — Beijing, China (Recruiting)

Study contacts

• Principal investigator: Junwei Hao, MD — Xuanwu Hospital, Beijing
• Study coordinator: Junwei Hao, MD

Conditions Acute Ischemic Stroke; acute ischemic stroke; extended time window; non-large vessel occlusion; intravenous thrombolysis