medwireNews: The thrombolytics tenecteplase and alteplase are comparable in terms of functional outcome and safety at 90 days after an acute ischemic stroke (AIS), according to the phase 3 ORIGINAL study.
An excellent functional outcome at 90 days, defined as a score of 0 or 1 (no symptoms or no significant disability) on the 6-point modified Rankin Scale (mRS), was achieved by 72.7% of patients receiving tenecteplase and 70.3% of those receiving alteplase.
This translated to a nonsignificant relative risk with tenecteplase versus alteplase of 1.03, with the lower bound of the 95% confidence interval above the 0.93 threshold for noninferiority.
“The overall treatment effect in this study of Chinese patients can be expected to be similar to other populations beyond China, given the comparability of the current result with existing studies, which comprise non-Asian populations across various stroke severities,” write Yongjun Wang (China National Clinical Research Center for Neurological Diseases, Beijing) and colleagues in JAMA.
Increasing clinical evidence supports the use of tenecteplase, “a bioengineered variant of alteplase with greater fibrin specificity and a longer half-life,” as a treatment option for patients with AIS; however, evidence for its benefits in Chinese AIS patients has been limited up to now, the researchers say.
The noninferiority study included adults across centers in China who had AIS with measurable neurologic deficit and a score of 1 to 25 points on the National Institutes of Health Stroke Scale (NIHSS), which ranges from 0 to 42 with higher scores indicating more severe symptoms. The patients were symptomatic for at least 30 minutes without significant improvement and were able to receive thrombolytic therapy within 4.5 hours of symptom onset.
The researchers randomly assigned the 1489 participants to receive intravenous treatment with either tenecteplase (n=732) or alteplase (n=733). Patients receiving tenecteplase were dosed at 0.25 mg/kg, up to a maximum dose of 25.0 mg, given as a bolus over 5 to 10 seconds. Meanwhile, those in the alteplase group received a dose of 0.9 mg/kg capped at 90 mg, with 10% of the dose administered as an initial bolus and the remainder immediately after as an infusion over a 1-hour period.
The median age of the participants was 66.0 years, 69.6% of the participants were men, and the median NIHSS score was 6.0 points. All but three patients received treatment within the 4.5-hour window, with 53% receiving it within 3 hours of stroke onset.
A similar proportion of patients in each treatment arm achieved an mRS score of 0–2 points at 90 days, at 80.9% of those given tenecteplase and 79.9% of those given alteplase. Wang et al note that significantly more patients aged 80 years or older in the tenectaplase group had excellent 90-day functional outcomes than their counterparts given alteplase (66.0% vs 26.1% respectively), but the researchers caution that the “sample size [n=93] was too small to draw meaningful conclusions.”
Neurologic improvement at 24 hours was seen in a corresponding 48.0% and 45.0% of participants in the tenecteplase and alteplase arms, which was signaled by an NIHSS score of 0 points or at least a 4-point improvement from baseline. The mean NIHSS score also fell at a similar rate between groups by day 90, with respective mean reductions from baseline of 3.70 and 3.02 points.
Meanwhile, Wang et al found no significant difference in the proportion of patients who achieved a 90-day score of at least 95 points on the Barthel Index, a 100-point measure of functional independence where lower scores indicate less independence, at 75.7% of patients given tenecteplase and 73.9% given alteplase.
In terms of safety, 1.2% of patients in each treatment group experienced symptomatic intracerebral hemorrhage, as defined by the European Cooperative Acute Stroke Study III, which led to the deaths of three patients in the tenecteplase group and five patients in the alteplase group. The rates of intracranial hemorrhage, as identified via cerebral imaging, were also similar, occurring in 8.1% and 8.6% of patients in the tenecteplase and alteplase groups, respectively.
Rates of all-cause mortality within 90 days of receiving treatment were 4.6% and 5.8% with tenecteplase and alteplase, respectively, with no significant difference in risk between the two. During the same period, Wang and colleagues found a similar proportion of patients with an mRS score of 5–6 points, at a corresponding 6.8% and 7.8%.
The investigators cited a number of limitations to the study. One was the open-label design, which could have influenced the post-procedural patient care, although Wang et al point out that the endpoint assessment was performed by a blinded reviewer. Another was the exclusion of data on stroke mimics, “which can be considered as part of routine acute stroke care,” they say.
Nevertheless, the authors conclude that their findings “provide evidence to support the use of tenecteplase as a suitable alternative to alteplase,” in patients with AIS.
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