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עברית
TAKE-HOME MESSAGE
TAKE-HOME MESSAGE- This randomized clinical trial assessed whether administering tenecteplase (TNK) beyond the standard-of-care time window improves outcomes in patients with large-/medium-vessel occlusion in the anterior circulation and salvageable tissue on perfusion imaging. More than three-fourths of the patients in this study underwent endovascular thrombectomy (EVT). There was no significant difference between TNK and placebo in the primary outcome (modified Rankin Scale score at 90 days). The secondary outcome, recanalization at 24 hours, was superior in the TNK group compared with the placebo group, but the other secondary efficacy outcomes were comparable between the groups. The safety outcomes were comparable between the groups. A subgroup analysis did not reveal any target population for a future trial, either.
- Although TNK administration was found to be safe and appeared to increase recanalization rates at 4.5 to 24 hours in patients with anterior-circulation large-/medium-vessel occlusion and salvageable tissue, it did not improve the functional outcomes, even in patients who did not undergo EVT.
BACKGROUND
Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited.
METHODS
We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage.
RESULTS
The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively.
CONCLUSIONS
Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups.
