Medium vessel occlusion (MeVO) accounts for 20-45% of acute ischemic stroke (AIS). Although patients with MeVO often present with relatively low NIHSS scores, up to one-third remain functionally dependent at follow-up despite receiving standard medical therapy, including intravenous thrombolysis. Recent randomized trials (DISTAL, ESCAPE-MeVO, DISCOUNT) have not demonstrated clinical benefit of endovascular treatment (EVT) for MeVO and have suggested higher risks of symptomatic intracranial hemorrhage and mortality, underscoring the need for safer and more targeted reperfusion strategies.
Intra-arterial thrombolysis (IAT) enables localized, high-concentration thrombolytic delivery with minimal mechanical manipulation, which may be advantageous for medium and distal vessels. Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA), a genetically engineered third-generation thrombolytic agent, has shown favorable pharmacologic properties and clinical safety in AIS, including in intra-arterial use following EVT. However, prospective evidence supporting its direct therapeutic role in MeVO-related AIS remains lacking.
This multicenter, prospective, open-label randomized controlled trial with blinded endpoint assessment is designed to evaluate the efficacy and safety of intra-arterial rhTNK-tPA thrombolysis in improving functional outcome in MeVO within 24 hours of symptom onset.
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)
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
Parallel
Intra-arterial Thrombolysis
Procedure/SurgeryrhTNK-tPA（Tenecteplase）dose: 0.125 mg/kg, maximum dose: 12.5mg.
Standard medical treatment
DrugStandard medical treatment
Excellent outcome
Rate of modified Rankin scale (mRS) 0-1 at 90±7 days
Ordinal distribution of mRS
The shift analysis of mRS at 90±7 days (mRS 5 and 6 merged)
Functional independence
Rate of mRS 0-2 at 90±7 days
Quality of life (EQ-5D-5L)
The EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) index score at 90±7 days The EQ-5D-5L is a standardized, preference-based measure of health-related quality of life covering five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with five severity levels. The EQ-5D-5L index score typically ranges from less than 0 (health states worse than death) to 1.0 (full health), with higher scores indicating better quality of life.
Neurologic deficit (NIHSS score) changes
The change of the National Institutes of Health Stroke Scale (NIHSS) score from baseline to 36±12 hours The NIHSS is a standardized clinical scale used to quantify neurologic impairment in stroke patients. The total score ranges from 0 to 42, with higher scores indicating more severe neurologic deficit. The outcome is defined as the change in NIHSS score from baseline, where a greater negative change reflects greater neurologic improvement.
Symptomatic intracranial hemorrhage (sICH)
Rate of sICH within 48 hours after randomization (Heidelberg Bleeding Classification)
All-caused mortality
All cause mortality at 90±7 days
Any intracranial hemorrhage
Rate of any intracranial hemorrhage within 48 hours after randomization (Heidelberg Bleeding Classification)
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Xiang Luo
Lead sponsor
Tongji Hospital
Sponsor institution
