Tenecteplase inferior to alteplase for moderate, severe acute ischemic stroke

In patients with moderate or severe ischemic stroke, a lower dose of IV tenecteplase yielded less favorable functional outcomes compared to a higher standard dose of alteplase, according to data published in The Lancet Neurology.

“Alteplase is the only approved thrombolytic drug in patients with acute ischemic stroke, although international guidelines have implemented tenecteplase as an alternative in highly specific subgroups,” Christopher Elnan Kvistad, PhD, of the department of neurology at Haukeland University Hospital in Norway, and colleagues wrote.

As a follow-up to the NOR-TEST trial, which determined that 0.4 mg/kg tenecteplase was comparable to 0.9 mg/kg of alteplase in safety and efficacy for patients with minor stroke, Kvistad and colleagues sought to establish non-inferiority of tenecteplase to alteplase, at the same doses, in patients with moderate or severe ischemic stroke.

The phase 3, randomized, open-label, blinded endpoint trial included 216 patients at 11 hospitals with stroke units in Norway between October 2019 and September 2021. Researchers randomized patients on a 1:1 basis to receive IV tenecteplase (0.4 mg/kg) or standard dose alteplase (0.9 mg/kg). The primary endpoint was a favorable functional outcome defined on a modified Rankin Scale score of 0-1 at 3 months, and all patients were subsequently followed up within 14 days of the 3-month follow-up.

Although the trial was prematurely halted for safety reasons, initial data showed a favorable functional outcome was reported less frequently in the tenecteplase group (31 of 96 patients) compared with alteplase (52 of 101 patients; OR = 0.45, 95% CI, 0.25-0.80).

In addition, intracranial hemorrhage was more frequent in those given tenecteplase (21 of 100 patients) compared with alteplase (7 of 104 patients, OR = 3.68; 95% CI, 1.49-9.11), and mortality at 3 months was also significantly higher with tenecteplase (15 of 96 patients) than with alteplase (5 of 101 patients, OR = 3.56; 95% CI, 1.24-10.21).

“Future stroke trial should assess a lower dose of tenecteplase versus alteplase in patients with moderate or severe stroke,” Kvistad and colleagues wrote.