More than 30% of the lower dose tenecteplase group achieved major reperfusion without symptomatic intracranial hemorrhage at 24 to 48 hours after thrombolysis.
Xin Cheng, MD, PhD
Findings from a phase 2a study (NCT04086147) showed that administration of tenecteplase between 4.5 to 24 hours from time of last known well is effective in achieving major reperfusion without symptomatic intracranial hemorrhage in patients with ischemic stroke.1,2
These data, presented at the 2022 International Stroke Conference (ISC), February 7-9, in New Orleans, Louisiana, indicate that tenecteplase seems feasible to extend the time window of IV thrombolysis to 24 hours after last known well through perfusion imaging selection. Based on these finding, investigators will move forward with examining the effects of the lower dose, 0.25 mg/kg, in a future phase 2b study.
"The stroke burden continues to grow across the world, and particularly in China where stroke is the leading cause of death,” lead investigator Xin Cheng, MD, PhD, associate professor of neurology, Huashan Hospital, Fudan University, said in a statement. "There are two major limitations in thrombolysis with alteplase: the restricted time window of 4.5 hours, and a low rate of success in re-opening arteries and restoring blood flow when a large brain vessel is blocked."1
A total of 86 patients, aged 18 to 80 years, were included in the open-label, blinded-end, Simon’s 2-stage, umbrella design study. In stage 1, a total of 18 patients were randomized to receive either 0.25 mg/kg or 0.32 mg/lg of recumbent human tenecteplase tissue plasminogen activator (rhTNK-tPA). Because more than 3 patients achieved the positive primary end point in either arm, the study continued to the second stage, where an additional 25 patients (43 in each dose strata) were included. The intervention dose was deemed to be of sufficient promise if 7 of the 43 patients achieved the positive primary outcome.2
The primary outcome, major reperfusion without symptomatic intracranial hemorrhage (sICH), was achieved in 14 of 43 patients (32.6%) in the lower dose tenecteplase group and in 10 of 43 patients (23.3%) in the higher dose group. Three months posttreatment, 53.5% of the patients were no more than slightly disabled, indicating that while not able to carry out all previous activities, they did not require daily assistance. Furthermore, 38.4% of participants either had no significant symptoms of residual neurological deficits or had mild symptoms but were able to return to pre-stroke activities of daily living.
Cheng added that, “tenecteplase appears to be safe and potent in reestablishing blood flow through blocked, large brain vessels, thereby preventing damage to brain tissue at risk of dying. Using perfusion imaging [to measure blood flow throughout the blood vessels] to assess patients with larger areas of potentially salvageable brain tissue and smaller areas that have already been lost to the stroke, it seems feasible that with tenecteplase we may be able to extend the time window for treatment to 24 hours after the time the patient was last known to be well. However, we still need more data from randomized controlled trials before practice changes to routinely include tenecteplase."1
On secondary outcomes, more patients in the higher dose group demonstrated 90-day modified Rankin Scale (mRS) scores between 0 to 1 and 0 to 2. Both groups had the same rates of recanalization (43.9%; n = 18 in each) 4 to 6 hours after treatment. Relative to the higher dose group (16.3%; n = 7), a slightly higher percentage of patients in the lower dose group (25.6%; n = 11) had 90-day mRS scores between 5 to 6.
An exploratory subgroup analysis compared outcomes in patients treated only with teneceplase (n = 52) or tenecteplase with endovascular therapy (EVT; n = 34). In this subset, fewer patients (8.8%; 3 of 34) who underwent treatment with both tenecteplase and endovascular therapy reached the primary outcome measure of restoring blood flow without symptomatic brain bleeding compared with those who received only tenecteplase (40.4%; 21 of 52).
“In our study, tenecteplase seems to be quite effective and safe in patients who do not need endovascular therapy,” Cheng said in a statement. “More research is needed to understand why tenecteplase was less effective in restoring blood flow and more likely to result in symptomatic brain bleeding among those who had endovascular therapy."1
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