Repeated Intravenous Thrombolysis for Ischemic Stroke With Medium to Large Vessel Occlusion Presenting Within 4.5 Hours of Onset With Tenecteplase (RITIS-TNK2)

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.