Background: EXTEND is a randomised, double-blind, placebo-controlled Phase III trial of intravenous alteplase vs. placebo among patients with ischemic stroke 4.5-9 hours from stroke onset or wake-up-stroke (WUS). There is uncertainty about the extent of salvageable tissue in this crucial time window for exploring therapeutic options. Whether WUS represents a plausible patient group for therapy is worthy exploring
Objective: To determine the penumbral mismatch and ischaemic core volumes in the EXTEND cohort and compare these characteristics between WUS and non-WUS subsets.
Methods: Patients with ischemic stroke within 4.5-9 hours from stroke onset and WUS patients (time of WUS onset defined as the midpoint between time to sleep and awakening with the stroke symptoms) are eligible for enrollment. Criteria for trial entry include perfusion-diffusion mismatch using a perfusion threshold of Tmax>6sec and a perfusion:diffusion lesion volume ratio of >1.2. Ischemic core must be <70mL based on assessment by automated RAPID software on MR or CT platforms (Stanford).
Results: 105 patients have been randomised to date with median age of 78.0 (IQR 66.5, 82 yrs), median admission NIHSS of 14.0 (8.0, 18.0) and half being female. WUS patients (n=69, 66%) compared to non-WUS patients, WUS patients had comparable median NIHSS of 14 (8, 18) vs 14.5 (8.0, 14.3 p =0.5), larger ischemic core volume of 15.5 ml (7.0, 33ml) vs 4.0 ml (0, 24.0ml p =0.005), perfusion deficit volume of 86.0 ml (58.5, 121.8ml) vs 73.0 ml (48.0, 124.0 ml p=0.6), mismatch ratio of 4.4 ml (2.6, 8.6 ml) vs 5.9 ml (2.7, 24.4 p=0.8) and mismatch volume of 64.0 ml (38.5, 91.8ml) vs 62.0 ml (42.5ml, 103.5ml p=0.5).
Conclusion: Within the EXTEND cohort, there is a clinically significant amount of salvageable penumbral tissue within the 4.5-9 hr time window. Patients with WUS have larger ischemic core compared to those in the non-WUS group. However, comparable salvageable mismatch volumes and baseline NIHSS are noted between groups. Tissue salvage has the potential to lead to clinical improvement in both groups.