While intravenous thrombolysis (IVT) within 4.5 hours is the standard medical reperfusion therapy, its efficacy is limited, particularly for large or medium vessel occlusions (LVO/MeVO), with low recanalization rates for IVT with rt-PA. The newer thrombolytic agent, tenecteplase (TNK), offers practical advantages-including single bolus administration, a longer half-life, and potentially higher fibrin specificity-and has been shown to be non-inferior to rt-PA.
Despite advances, a significant proportion of patients with LVO/MeVO do not achieve early clinical improvement after standard IVT, likely due to persistent occlusion from a high thrombus burden. Endovascular therapy, while highly effective for LVO, has limited accessibility. Therefore, there is an urgent need for more effective and widely accessible pharmacological strategies.
This study proposes a rescue strategy based on the hypothesis that a second dose of IVT may improve outcomes in patients with imaging-confirmed LVO or MeVO who show no significant neurological improvement one hour after standard TNK thrombolysis (administered within 4.5 hours of stroke onset). The primary aim of this study is to formally evaluate the efficacy and safety of a repeated dose of intravenous tenecteplase in this specific patient population.
Age ≥ 18 year;
Acute ischemic stroke presumably caused by large or medium vessel occlusion within 4.5 hours of onset, having received standard-dose intravenous thrombolysis, and with no planned thrombectomy;
Measurable neurological deficit before the first intravenous thrombolysis, with NIHSS ≥ 4;
Baseline pc-ASPECTS/ASPECTS ≥ 6, and for posterior circulation infarction, a Pontine-Midbrain Index ≤ 2 (assessed by CT or DWI);
Planed for endovascular treatment;
Significant white matter hyperintensities (Fazekas score 3);
Any coagulation abnormality before the first thrombolysis, including INR > 1.5;
Receipt of dual antiplatelet therapy within 24 hours prior to thrombolysis.；
Parallel
Tenecteplase
DrugTenecteplase is administered intravenously at a dose of 16 mg, with a maximum dose of 0.25 mg/kg.
rate of vessel recanalization
proportion of excellent functional outcome (modified Rankin Scale (mRS) 0-1)
The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome
proportion of favorable functional outcome (modified Rankin Scale (mRS) 0-2)
The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome
ordinal distribution of modified Rankin Scale (mRS)
The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome
occurrence of early neurological improvement (ENI)
ENI is defined as more than 4-point decrease in National Institute of Health stroke scale score; the minimum and maximum values of NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome
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