Abstract
Introduction: Penumbral imaging-based selection of patients for thrombolysis with tenecteplase (TNK) has been shown to be feasible up to 6 h after onset. We aimed to demonstrate the feasibility and safety of thrombolysis in ischemic stroke patients with penumbral patterns presenting 4.5-24 h after symptom onset. Methods: We conducted an open label single arm trial. Acute ischemic stroke patients presenting between 4.5-24 h after symptom onset were assessed with perfusion imaging. Patients with pretreatment perfusion CT/MRI that demonstrated a perfusion deficit volume >15 ml and penumbra volume >20% of the infarct core were eligible for TNK treatment. They received 0.25 mg/kg IV TNK. The primary outcome was symptomatic hemorrhagic transformation. Patients screened with perfusion CT/MRI who met trial criteria, but were not enrolled in the study, formed a parallel cohort. Results: A total of 26 patients were screened with perfusion CT/MRI. Thirteen patients received TNK (mean±SD age = 62±12 y). The 13 parallel cohort patients were of similar age (55±18 y, p=0.257). Median (IQR) baseline NIHSS in TNK treated patients (13(9)) was similar to that in the parallel cohort (14(10), p=1.00). Median time to TNK treatment was 8.7 h(range: 5.1-23.3). Reperfusion and recanalization occurred in 54.5% and 50% of TNK treated patients at 24 h, respectively. Infarct growth at 24 h was attenuated in TNK treated patients (8.7 (31.3) ml) relative to the parallel cohort (53.0 (91.5) ml, p=0.017). Penumbral salvage volume was greater in TNK treated patients (51.7 (58.2) ml) than parallel cohort patients (-16.7 (112.2) ml, p=0.001). There was one symptomatic hemorrhage in the TNK group (ECASS grade PH1). Two other TNK treated patients developed asymptomatic hemorrhages (ECASS grade PH1). The rate of good functional outcome (modified Rankin Score ≤2) at day 90 was greater in TNK patients (8/12, 66.7%) than in the parallel cohort (2/13, 15.3%, p=0.015). Conclusion: Thrombolysis with TNK treatment in appropriately selected patients is feasible even up to 24 hours after onset. Randomized studies of penumbral imaging-based selection of TNK candidates in an extended therapeutic time window are warranted.
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