Intra-arterial recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) thrombolysis for acute medium vessel occlusion (MeVO-TNK): Study rationale and design

The optimal management of acute ischemic stroke caused by medium vessel occlusion (MeVO) remains uncertain. Recent randomized trials have failed to demonstrate a clear benefit of endovascular therapy in this population, whereas intra–arterial thrombolysis (IAT) has emerged as a biologically plausible alternative. However, prospective evidence supporting IAT in MeVO is lacking, and the optimal dosing strategy for stand–alone IAT remains undefined.

Aim

To preliminarily evaluate the efficacy and safety of intra–arterial tenecteplase (IA–TNK) plus standard medical therapy (SMT) compared with SMT alone in patients with acute MeVO stroke, and to explore a stepwise IA–TNK dosing strategy.

Design

The MeVO–TNK trial is a multicenter, prospective, randomized, open–label, blinded–endpoint (PROBE), exploratory phase II study. A total of 60 participants with imaging–confirmed MeVO will be randomized 1:1 to receive either IA–TNK plus SMT or SMT alone. Participants presenting beyond 6 hours from symptom onset must demonstrate salvageable penumbral tissue on advanced imaging. Those assigned to the intervention group will receive up to two intra–arterial boluses of tenecteplase (0.0625 mg/kg per bolus), with the second bolus administered based on angiographic assessment of reperfusion and safety.

Outcomes

The primary efficacy outcome is final infarct volume measured at 72 ± 24 hours after randomization. Secondary efficacy outcomes include the proportions of patients achieving modified Rankin Scale (mRS) scores of 0–1, 0–2 and 0–3 at 90 days, a shift analysis of the mRS distribution at 90 days, early neurological deterioration, and National Institutes of Health Stroke Scale score at 7 days or discharge. The primary safety outcome is symptomatic intracranial hemorrhage within 24 hours.

Conclusions

This trial will provide preliminary evidence on the biological efficacy, reperfusion potential and safety of stand–alone IA–TNK for acute MeVO stroke, helping to address an important evidence gap and inform the design of future confirmatory studies.

Trial Registration

Chinese Clinical Trial Registry, ChiCTR2400091249.

WHAT IS ALREADY KNOWN ON THIS TOPIC

The optimal reperfusion strategy for medium vessel occlusion (MeVO) remains uncertain, and no randomized trial has specifically evaluated intra-arterial tenecteplase (IA-TNK) as a stand-alone treatment for acute MeVO stroke.

WHAT THIS STUDY ADDS

The MeVO-TNK trial is a multicenter randomized study that will assess the efficacy and safety of IA-TNK plus standard medical therapy versus standard medical therapy alone and explore a stepwise IA-TNK dosing strategy.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

The findings will provide preliminary evidence to guide future definitive trials and may support the development of alternative reperfusion strategies for patients with MeVO.