Intra-arterial Recombinant Human Tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA) Thrombolysis for Acute Medium Vessel Occlusion

This study is an investigator-initiated, multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) clinical trial designed to evaluate the efficacy and safety of intra-arterial rhTNK-tPA in improving 90-day functional outcomes in patients with MeVO stroke within 24 hours of symptom onset. The primary outcome is the proportion of patients achieving a modified Rankin Scale (mRS) score of 0-1 at 90 days. Eligible patients will be randomized in a 1:1 ratio to receive either intra-arterial rhTNK-tPA thrombolysis (0.125 mg/kg, Max 12.5mg) plus standard medical therapy or standard medical therapy alone. A total of 382 participants (191 per group) will be enrolled in this trial.

Inclusion criteria

• Age ≥18 years
• Pre-stroke mRS score 0-1
• Baseline NIHSS ≥4 or symptoms deemed clearly disabling by treating physician (e.g., hemianopia, aphasia, or motor dysfunction)
• Isolated medium distal vessel occlusion (i.e., an occlusion of the co-/non-dominant M2, the M3/M4 segment of the MCA, the A1/A2/A3 segment of the ACA or the P1/P2/P3 segment of the PCA) confirmed by CT angiography (CTA) or MR angiography (MRA)
• Acute ischemic stroke within 24 hours of symptom onset, including wake-up stroke or unwitnessed stroke; The onset time of symptoms was defined as the last time of normal performance.
• Acute ischemic stroke within 6-24 hours of onset, meeting at least one of the following imaging criteria:

• Evidence of a hypoperfusion-ischemic core mismatch on CT or MRI perfusion, defined as an ischemic core volume <50mL, hypoperfused tissue volume to ischemic core volume ratio ≥1.2, and mismatch volume ≥10 mL
• Evidence of a diffusion-hyperintensity mismatch, defined as absence of hyperintensity on fluidattenuated inversion recovery (FLAIR) imaging within ≥ 90% of the area of the diffusion weighted imaging (DWI) lesion)
• The participant or legally authorized representative is capable of providing informed consent

Exclusion criteria

• Evidence of intracranial hemorrhage
• Any active bleeding (gastrointestinal, urinary, hemorrhagic retinopathy, etc.) or parenchymal organ surgery or biopsy within 30 days before stroke; Severe head trauma or stroke within the past 3 months
• Persistent and uncontrolled hypertension, defined as systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg
• Inherited or acquired hemorrhagic tendancy; deficiency of anticoagulant factors; or on oral anticoagulant with an INR> 1.7
• Blood glucose <2.8 mmol/L (50 mg/dl) or > 22.2mmol/L (400 mg/dl), platelets count <100*109/L, or hemoglobin <70g/L
• Severe hepatic insufficiency, chronic hemodialysis and severe renal insufficiency (or recent blood tests suggesting a glomerular filtration rate <30 ml/min or blood creatinine> 200 mmol/L (2.5 mg/dl)
• Women who are pregnant or breastfeeding
• Allergy to rhTNK-tPA or radiocontrast agent
• Participation in other clinical trials
• Expected survival time less than 6 months (e.g., due to malignancy, severe cardiopulmonary disease, etc.)
• Other conditions deemed by the investigator to make the patient unsuitable for participation or pose significant risks (e.g., inability to understand and/or comply with study procedures and/or follow-up due to mental illness, cognitive or emotional disorders)