The following is a summary of the “Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomized controlled trial,” published in the February 2023 issue of Neurology by Roaldsen, et al.
Clinical guidelines and current evidence both advocate intravenous thrombolysis with alteplase for patients with wake-up stroke who have been identified for treatment using magnetic resonance imaging or perfusion imaging. However, there is typically a lack of availability for high-tech imaging methods. Researchers wanted to ascertain if the functional outcome is improved in patients with ischemic wake-up stroke chosen by non-contrast CT if thrombolytic treatment with intravenous tenecteplase is administered within 4–5 h of awakening. The TWIST study involved 77 hospitals in 10 countries and was an investigator-initiated multicenter open-label randomized controlled experiment with blinded endpoint assessment. Patients were eligible if they were 18 or older, woke up with symptoms of acute ischaemic stroke, such as limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher, or aphasia, had a non-contrast CT of the head, and could receive tenecteplase within 4–5 hours of awakening. Patients were allocated to receive either a single intravenous bolus of tenecteplase 0.25 mg per kg of body weight (maximum 25 mg) or control (no thrombolysis) based on a central, web-based, computer-generated randomization schedule (1:1).
Research assistants were blinded to participants’ treatment assignments when they called them 90 days later to perform follow-up interviews. Upon admission to the hospital, clinical evaluations were conducted on Day 1 (for baseline purposes) and on Day 7 (or at discharge, whichever occurred first). In the study’s primary analysis, the 90-day functional outcome on the modified Rankin Scale (mRS) was analyzed with intention-to-treat population ordinal logistic regression. About 578 out of the required 600 individuals were enrolled between June 12, 2017, and September 30, 2021. (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). Participants’ median ages ranged from 737 to 811. Out of the total of 578 people, 332 (57%) were male and 246 (43%) were female.
According to the modified Rankin Scale (mRS) at 90 days, tenecteplase treatment was not related with better functional outcome. (Adjusted OR = 1.18; 95% CI = 0.88-1.58; p = 0.27). There was no statistically significant difference in the 90-day mortality rate between the tenecteplase and control groups (28 patients (10%) in the tenecteplase group and 23 patients (8%) in the control group; adjusted HR 1.29, 95% CI 0.74-2.26; P=0.37). About 6 patients in the tenecteplase group (2%) and 3 patients in the control group (1%) experienced symptomatic intracranial haemorrhage (adjusted OR 217, 95% CI 053-887; P=028), while 33 patients in the tenecteplase group (11%) and 30 patients in the control group (10%) experienced any intracranial haemorrhage (adjusted OR 114). Treatment with tenecteplase was not related with improved functional outcome at 90 days in patients with wake-up stroke who were chosen using non-contrast CT. Previous trials of wake-up stroke patients screened with sophisticated imaging have shown that the number of symptomatic haemorrhages and any intracranial haemorrhages in both therapy groups is comparable. Patients identified using non-contrast CT do not currently have sufficient evidence to warrant treatment with tenecteplase.