Abstract Body: Patients with AIS caused by large vessel occlusion (LVO) treated in the extended time window obtained better outcomes with tenecteplase (TNK) versus tPA regarding arterial reperfusion and clinical outcomes. None of these trials compared TNK in non-LVO AIS in the extended time window using clinical-radiological mismatch or CTP. Prospective, multicenter, randomized, controlled, double-blinded trial. The randomization employs a 1:1 ratio of intravenous thrombolysis with TNK versus placebo in patients who suffer a non-LVO AIS between 4.5 and 12 hours from the TLSW and have evidence of salvageable brain with a clinical-radiological mismatch. The primary outcome is the rate of good clinical outcome using sliding dichotomy (mRS 0-1 for baseline mRS 0; mRS ≤ 2 for baseline mRS 1) as evaluated by two separate assessors at the central core lab, with local reading as a backup. The study recruitment is ongoing, with the final analysis planned for 2026, including 360 patients with completed 90-day follow-ups. Enrollment is ongoing at sites. Until October 2024, 89 patients have been enrolled. The RESILIENT EXTEND-IV trial may provide inputs on the efficacy and safety of TNK use in non-LVO AIS in the extended time window.