ABSTRACT
RATIONALE: To date, the benefit of intravenous thrombolysis for acute ischemic stroke (AIS) patients without advanced neuroimaging selection is confined to within 4.5 h of onset. Our phase II EXIT-BT (Extending the tIme window of Thrombolysis by ButylphThalide up to 6 h after onset) trial suggested the safety, feasibility, and potential benefit of intravenous tenecteplase (TNK) in AIS between 4.5 and 6 h of onset. The EXIT-BT2 trial is a pivotal study undertaken to confirm or refute this signal. AIM: To investigate the efficacy and safety of TNK for AIS between 4.5 and 6 h of onset with or without endovascular treatment. SAMPLE SIZE ESTIMATES: A maximum of 1440 patients are required to test the superiority hypothesis with 80% power according to a two-sided 0.05 level of significance, stratified by age, sex, history of diabetes, location of vessel occlusion, baseline National Institute of Health stroke scale score, stroke etiology, and plan for endovascular treatment. DESIGN: EXIT-BT2 is a prospective, randomized, open-label, blinded assessment of endpoint (PROBE), and multi-center study. Eligible AIS patients between 4.5 and 6 h of onset are randomly assigned 1:1 into a TNK group or control group. The TNK group will receive TNK (0.25 mg/kg, a single bolus over 5-10 s, maximum 25 mg). The control group will receive standard medical care in compliance with national guidelines for acute ischemic stroke. Both groups will receive standard stroke care from randomization to 90 days after stroke onset according to national guidelines. OUTCOME: The primary efficacy endpoint is excellent functional outcome, defined as a modified Rankin Scale score 0-1 at 90 days after randomization, while the primary safety endpoint is symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale score increase ⩾4 caused by intracranial hemorrhage within 24 (-6/+12) h after randomization. CONCLUSIONS: The results of EXIT-BT2 may determine whether intravenous TNK has a favorable risk/benefit profile in AIS between 4.5 and 6 h of onset.
ABSTRACT
Background: Intravenous recombinant tissue plasminogen activator (r-tPA) with 0.9 mg/kg is the standard treatment for acute ischemic stroke, but it remains unclear whether it is optimal for all patients. We aimed to determine the optimal dose of r-tPA for Chinese stroke based on the data from the INTRECIS study. Methods: From the INTRECIS cohort, patients receiving intravenous r-tPA within 4.5 h of onset were included. According to r-tPA dose, patients were assigned into seven groups (from 0.60 to 0.90 mg/kg). The primary outcomes were the proportion of excellent functional outcomes and symptomatic intracranial hemorrhage. Results: Overall, 2,666 patients were included: 156 in 0.60 mg/kg group, 117 in 0.65 mg/kg group, 127 in 0.70 mg/kg group, 188 in 0.75 mg/kg group, 154 in 0.80 mg/kg group, 359 in 0.85 mg/kg group, and 1,565 in 0.90 mg/kg group. After adjustment for baseline characteristics, only 0.65 mg/kg group had significantly higher proportion of excellent functional outcome than 0.90 mg/kg group (79.5 vs. 71.4%, odds ratio = 1.833, 95% CI = 1.006-3.341, adjusted p = 0.048). The subgroup analysis showed no evidence of differences in the odds of having a primary outcome between the two groups by age, admission NIHSS, onset to thrombolysis time, and TOAST classification. There was no significant difference in symptomatic intracranial hemorrhage between groups. Conclusion: Our study presented the first evidence that intravenous thrombolysis with 0.65 mg/kg r-tPA may be optimal for Chinese mild-to-moderate stroke. Registration: https://www.clinicaltrials.gov, identifier: NCT02854592.