medwireNews: Giving tenecteplase 4.5 to 24.0 hours after large vessel occlusion of the middle cerebral or internal carotid artery to patients who do not have access to immediate endovascular thrombectomy reduces disability compared with standard medical therapy, shows the TRACE-III trial.
“These results can be viewed in the context of the TIMELESS trial , which did not show a benefit of tenecteplase in similar patients with stroke, most of whom underwent endovascular thrombectomy immediately after receiving thrombolytic therapy,” say the researchers Youngjun Wang (Beijing Tiantan Hospital, China) and colleagues in The New England Journal of Medicine.
They point out that in the current phase 3 trial, fewer than 2% of patients underwent rescue endovascular thrombectomy.
Wang et al enrolled 516 patients who had experienced an ischemic stroke involving middle cerebral artery or internal carotid artery and had salvageable brain tissue from 58 centers in China between 2022 and 2023. The patients had a median age of 67 years, 67.8% were men, and the median score on the National Institutes of Health Stroke Scale (NIHSS), where higher scores indicate greater neurological deficits, was 10 points out of a possible 42 points.
The participants were randomly assigned to receive either bolus tenecteplase at a dose of 0.25 mg/kg up to a maximum of 25 mg/kg (n=264) or standard antiplatelet therapy (n=252) within 4.5 to 24.0 hours of last being well.
“[E]xtending the initiation of treatment to 24 hours after stroke onset more than doubled the number of patients who were eligible for participation,” the researchers highlight.
Rescue endovascular thrombectomy was needed by four patients in the tenecteplase group and five in the standard treatment group.
At the 90-day follow up, 33.0% of patients in the tenecteplase group met the primary endpoint of a modified Rankin Scale (mRS) score of 0–1 points (where 0 equals no disability), compared with 24.2% of those who received standard therapy, a significant difference.
In addition, significantly more patients in the tenecteplase group than the standard therapy group had major neurological improvement at 72 hours, defined as an NIHSS score of 1 point or below or at least an 8-point reduction from baseline, at 16.0% versus 6.0%, and were functionally independent (mRS ≤2 points) at 90 days, at 43.6% versus 33.3%.
The two treatment groups had similar mortality rates, at 13.3% and 13.1% in the tenecteplase and standard therapy groups, respectively. However, rates of symptomatic intracranial hemorrhage within 36 hours of treatment were numerically, albeit not significantly, higher among those treated with tenecteplase, at 3.0% versus 0.8%. This was also the case for moderate or severe systemic bleeding within 90 days (1.9 vs 0.8%) and any serious adverse event (20.1 vs 17.1%).
Wang et al point out that that while the effect size with tenecteplase versus standard therapy after 4.5 hours in their study was similar to that previously reported for thrombolytic therapy given at 0–3 hours after stroke, it was smaller than that seen with thrombectomy.
Nevertheless, they say that the results “support the use of tenecteplase in the extended time window when endovascular thrombectomy is not immediately available.”
The researchers suggest, however, that the findings should be corroborated in trials performed outside of China, “where intracranial atherosclerosis is more prevalent than in Western countries and atrial fibrillation is less prevalent.”
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