medwireNews: Treatment with the thrombolytic tenecteplase between 4.5 and 24.0 hours after stroke onset provides no functional benefit for patients with occlusions of the middle cerebral artery or internal carotid artery, the TIMELESS trial has found.
At 90 days after treatment, patients given tenecteplase at 0.25 mg per kg of bodyweight (maximum dose 25 mg) had similar clinical outcomes to those given placebo, with both groups scoring a median of 3 points out of a possible 6 points on the modified Rankin scale (where a higher score indicates greater disability). This corresponded to an adjusted common odds ratio of 1.13.
Tenecteplase is a modified form of human tissue plasminogen activator, write Gregory Albers (Stanford Stroke Center, Palo Alto, California, USA) and colleagues in The New England Journal of Medicine. They note that while the treatment can be used as an alternative to alteplase within 4.5 hours of stroke onset in some patients, data regarding its use beyond 4.5 hours were “limited” prior to this study.
The trial enrolled stroke patients with a National Institutes of Health Stroke Scale (NIHSS) score of at least 5 points (ranging from 0 to 42 points, with a higher score indicating worse neurologic deficits) attributed to occlusions of the middle cerebral or the internal carotid artery. All the participants had perfusion imaging evidence of salvageable brain tissue.
In all, 228 patients received intravenous tenecteplase a median of 12.3 hours after last being known to be well compared with 12.7 hours among the 230 patients given placebo. The median ages of the patients were 72 years and 73 years, respectively, and 53.5% were women and 74.0% were White. The median baseline NIHSS score was 12 points in both groups.
The researchers note that the majority (77.3%) of patients did subsequently undergo endovascular thrombectomy, which was anticipated for patients with occlusions of the internal carotid artery (n=37) or the M1 segment (n=227) and at the discretion of the treating physician for those with occlusions of the M2 segment (n=173).
With regard to safety, mortality at 90 days did not differ significantly between patients taking tenecteplase and those taking placebo, with rates of 19.7% versus 18.2%, and nor did symptomatic intracerebral hemorrhage, occurring in 3.2% and 2.3%.
Complete recanalization at 24 hours “appeared to be higher with tenecteplase than with placebo, but the incidence of reperfusion was similar in the two groups at the end of the procedure,” the team observes, noting that this secondary outcome was not adjusted for multiplicity.
In an editorial related to the study, Dana Leifer (Weill Cornell Medical College, New York, USA) says the findings suggest that administering tenecteplase in the 4.5 to 24.0-hour window is “probably unlikely to help patients who present with large-vessel occlusions and do not undergo thrombectomy.”
She adds that “[a]dditional trials may determine whether tenecteplase administered at more than 4.5 hours after symptom onset benefits subgroups of patients who are expected to undergo thrombectomy or who do not have large-vessel occlusions.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group
N Eng J Med 2024; 390: 701–711
N Eng J Med 2024; 390: 760–761