Effect of Time to Thrombolysis on Clinical Outcomes in Patients With Acute Ischemic Stroke Treated With Tenecteplase Compared to Alteplase: Analysis From the AcT Randomized Controlled Trial
Bibliographic record
Abstract
BACKGROUND: The AcT (Alteplase Compared to Tenecteplase) randomized controlled trial showed that tenecteplase is noninferior to alteplase in treating patients with acute ischemic stroke within 4.5 hours of symptom onset. The effect of time to treatment on clinical outcomes with alteplase is well known; however, the nature of this relationship is yet to be described with tenecteplase. We assessed whether the association of time to thrombolysis treatment with clinical outcomes in patients with acute ischemic stroke differs by whether they receive intravenous tenecteplase versus alteplase. METHODS: Patients included were from AcT, a pragmatic, registry-linked, phase 3 randomized controlled trial comparing intravenous tenecteplase to alteplase in patients with acute ischemic stroke. Eligible patients were >18 years old, with disabling neurological deficits, presenting within 4.5 hours of symptom onset, and eligible for thrombolysis. Primary outcome was modified Rankin Scale score 0 to 1 at 90 days. Safety outcomes included 24-hour symptomatic intracerebral hemorrhage and 90-day mortality rates. Mixed-effects logistic regression was used to assess the following: (a) the association of stroke symptom onset to needle time; (b) door (hospital arrival) to needle time with outcomes; and (c) if these associations were modified by type of thrombolytic administered (tenecteplase versus alteplase), after adjusting for age, sex, baseline stroke severity, and site of intracranial occlusion. RESULTS: Of the 1538 patients included in this analysis, 1146 (74.5%; 591 tenecteplase and 555 alteplase) presented within 3 hours versus 392 (25.5%; 196: TNK and 196 alteplase) who presented within 3 to 4.5 hours of symptom onset. Baseline patient characteristics in the 0 to 3 hours versus 3- to 4.5-hour time window were similar, except patients in the 3- to 4.5-hour window had lower median baseline National Institutes of Health Stroke Severity Scale (10 versus 7, respectively) and lower proportion of patients with large vessel occlusion on baseline CT angiography (26.9% versus 18.7%, respectively). Type of thrombolytic agent (tenecteplase versus alteplase) did not modify the association between continuous onset to needle time ( P interaction =0.161) or door-to-needle time ( P interaction =0.972) and primary clinical outcome. Irrespective of the thrombolytic agent used, each 30-minute reduction in onset to needle time was associated with a 1.8% increase while every 10 minutes reduction in door-to-needle time was associated with a 0.2% increase in the probability of achieving 90-day modified Rankin Scale score 0 to 1, respectively. CONCLUSIONS: The effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes. REGISTRATION: URL: https://classic.clinicaltrials.gov ; Unique identifier: NCT03889249.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.014 | 0.026 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.010 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".