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A Randomized Trial of Tenecteplase Versus Alteplase for Acute Ischemic Stroke
Study Questions:
What is the comparative efficacy of the standard dose of alteplase with two different doses of tenecteplase?
Methods:
In this phase 2B trial, the investigators randomly assigned 75 patients to receive alteplase (0.9 mg/kg of body weight) or tenecteplase (0.1 mg/kg or 0.25 mg/kg) less than 6 hours after the onset of ischemic stroke. To favor the selection of patients most likely to benefit from thrombolytic therapy, the eligibility criteria were a perfusion lesion at least 20% greater than the infarct core on computed tomographic (CT) perfusion imaging at baseline and an associated vessel occlusion on CT angiography. The coprimary endpoints were the proportion of the perfusion lesion that was reperfused at 24 hours on perfusion-weighted magnetic resonance imaging and the extent of clinical improvement at 24 hours, as assessed on the National Institutes of Health Stroke Scale (NIHSS, a 42-point scale on which higher scores indicate more severe neurologic deficits).
Results:
The three treatment groups each comprised 25 patients. The mean (± SD) NIHSS score at baseline for all patients was 14.4 ± 2.6, and the time to treatment was 2.9 ± 0.8 hours. Together, the two tenecteplase groups had greater reperfusion (p = 0.004) and clinical improvement (p < 0.001) at 24 hours than the alteplase group. There were no significant between-group differences in intracranial bleeding or other serious adverse events. The higher dose of tenecteplase (0.25 mg/kg) was superior to the lower dose and to alteplase for all efficacy outcomes, including absence of serious disability at 90 days (in 72% of patients, vs. 40% with alteplase; p = 0.02).
Conclusions:
The authors concluded that tenecteplase was associated with significantly better reperfusion and clinical outcomes than alteplase in patients with stroke.
Perspective:
The current study reports that, using CT perfusion and angiographic imaging to select patients for thrombolytic treatment of acute ischemic stroke, tenecteplase was superior to alteplase with respect to the coprimary endpoints of reperfusion and clinical improvement at 24 hours. Furthermore, the improved reperfusion and clinical response with tenecteplase did not come at a cost of increased intracranial hemorrhage. These positive findings, while encouraging, should be considered preliminary, due to the small sample size of the study. Another caveat is that a large number of patients who are currently eligible for thrombolysis on the basis of standard clinical and noncontrast CT criteria were excluded from this trial because of these additional imaging selection requirements. A large phase 3 study is indicated to determine whether the efficacy of tenecteplase extends to this broader population of patients.
Keywords: Thrombolytic Therapy, Stroke, Intracranial Hemorrhages, National Institutes of Health (U.S.), Fibrinolytic Agents, Tissue Plasminogen Activator, Magnetic Resonance Imaging, Perfusion Imaging, United States
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