Tenectaplase versus Alteplase before Thrombectomy for Ischemic Stroke: EXTEND-IA TNK Trial


EXTEND-IA TNK is a multicenter, randomized, open-label, blinded-outcomes, non-inferiority trial of acute ischemic stroke patients with internal carotid, middle cerebral, or basilar artery occlusion eligible for both intravenous thrombolysis. Patients were randomized 1:1 to receive IV tenecteplase (0.25mg/kg; max dose 25mg) or IV alteplase (0.9mg/kg; max dose 90mg). A blinded adaptive sample-size estimation helped determine the final sample size of 202. From 2015-2017, across 12 centers in Australia and New Zealand, 101 patients were assigned to each arm. The primary outcome of “substantial reperfusion” defined as reperfusion in >50% of the compromised vascular territory or the absence of the retrievable thrombus at the time of initial angiography was achieved in 22% of patients in tenectaplase group compared to 10% in alteplase group (p=0.002 for noninferiority; p=0.03 for superiority). At 90 days, patients in tenectaplase group had better functional status with median mRS of 2 compared to 3 in alteplase group (p=0.04). Symptomatic intracerebral hemorrhage occurred in one patient in each group. High fibrin specificity and longer half-life permitting bolus administration of the total dose, makes this genetically modified variant of alteplase a practical choice especially for inter-facility transfer patients. The EXTEND-IA TNK Part 2 studying the higher 0.4mg/kg tenectaplase dose and the TASTE trial comparing tenectaplase to alteplase in non-thrombectomy stroke patients would provide further information in near future. Current evidence suggests tenectaplase is a safe, effective and practical alternative to alteplase before thrombectomy in acute ischemic stroke patients.

Andrew W. Grande, MD
Minneapolis, MN
Shailesh Male, MD
Minneapolis, MN