BACKGROUND: Recent randomized trials demonstrated the beneficial effect of endovascular therapy in patients with low Alberta Stroke Program Early CT Score. Despite large follow-up infarct volumes, a significantly increased rate of good functional outcomes was observed, challenging the role of infarct volume as a predictive imaging marker. This analysis evaluates the extent to which the effects of endovascular thrombectomy on functional outcomes are explained by (1) follow-up infarct volume and (2) early neurological status in patients with stroke with low Alberta Stroke Program Early CT Score. METHODS: TENSION (Efficacy and Safety of Thrombectomy in Stroke With Extended Lesion and Extended Time Window) was a randomized trial conducted from February 2018 to January 2023 across 41 stroke centers. Two hundred fifty-three patients with ischemic stroke due to anterior circulation large vessel occlusion and Alberta Stroke Program Early CT Score of 3 to 5 were randomized to endovascular thrombectomy plus medical treatment or medical treatment alone. All patients with the availability of relevant data points were included in this secondary as-treated analysis. The primary outcome was the 90-day modified Rankin Scale score. Confounder-adjusted mediation analysis was performed to quantify the proportion of the treatment effect on a 90-day modified Rankin Scale score explained by (1) 24-hour follow-up infarct volume and (2) 24-hour National Institutes of Health Stroke Scale scores. RESULTS: One hundred eighty-eight patients were included; thereof, 87 (46%) were female patients. Median age was 72 (interquartile range, 63-79) years. The endovascular thrombectomy cohort had a 20.5 (95% CI, 8.3-33.7) percentage points higher probability of achieving independent ambulation (modified Rankin Scale, 0-3) and a 24.2 (95% CI, 13.4-35.8) percentage points lower mortality at 90 days compared with medical treatment alone. The reduction in 24-hour follow-up infarct volume explained 30% of the treatment effect on functional outcomes, while the 24-hour National Institutes of Health Stroke Scale score explained 61%. CONCLUSIONS: In patients with low Alberta Stroke Program Early CT Score, infarct volume demonstrated limited explanatory power for functional outcomes compared with the early neurological status, which may more effectively reflect factors such as the involvement of specific brain regions, disruption of structural networks, and selective neuronal loss.
- MeSH
- endovaskulární výkony metody MeSH
- ischemická cévní mozková příhoda * chirurgie diagnostické zobrazování MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- trombektomie * metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
RATIONALE: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs. AIMS: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion. METHODS AND DESIGN: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial. STUDY OUTCOMES: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted. SAMPLE SIZE: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation. DISCUSSION: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia. TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31.
- MeSH
- endovaskulární výkony * metody MeSH
- ischemická cévní mozková příhoda * komplikace diagnóza MeSH
- ischemie mozku * komplikace MeSH
- klinické zkoušky, fáze II jako téma MeSH
- kvalita života MeSH
- kyslík terapeutické užití MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- trombektomie metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- protokol klinické studie MeSH
BACKGROUND: Recent evidence suggests a beneficial effect of endovascular thrombectomy in acute ischaemic stroke with large infarct; however, previous trials have relied on multimodal brain imaging, whereas non-contrast CT is mostly used in clinical practice. METHODS: In a prospective multicentre, open-label, randomised trial, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and a large established infarct indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 were randomly assigned using a central, web-based system (using a 1:1 ratio) to receive either endovascular thrombectomy with medical treatment or medical treatment (ie, standard of care) alone up to 12 h from stroke onset. The study was conducted in 40 hospitals in Europe and one site in Canada. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days, assessed by investigators masked to treatment assignment. The primary analysis was done in the intention-to-treat population. Safety endpoints included mortality and rates of symptomatic intracranial haemorrhage and were analysed in the safety population, which included all patients based on the treatment they received. This trial is registered with ClinicalTrials.gov, NCT03094715. FINDINGS: From July 17, 2018, to Feb 21, 2023, 253 patients were randomly assigned, with 125 patients assigned to endovascular thrombectomy and 128 to medical treatment alone. The trial was stopped early for efficacy after the first pre-planned interim analysis. At 90 days, endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better outcome (adjusted common OR 2·58 [95% CI 1·60-4·15]; p=0·0001) and with lower mortality (hazard ratio 0·67 [95% CI 0·46-0·98]; p=0·038). Symptomatic intracranial haemorrhage occurred in seven (6%) patients with thrombectomy and in six (5%) with medical treatment alone. INTERPRETATION: Endovascular thrombectomy was associated with improved functional outcome and lower mortality in patients with acute ischaemic stroke from large vessel occlusion with established large infarct in a setting using non-contrast CT as the predominant imaging modality for patient selection. FUNDING: EU Horizon 2020.
- MeSH
- cévní mozková příhoda * diagnostické zobrazování chirurgie MeSH
- endovaskulární výkony * metody MeSH
- infarkt komplikace MeSH
- intrakraniální krvácení etiologie MeSH
- ischemická cévní mozková příhoda * diagnostické zobrazování chirurgie MeSH
- ischemie mozku * diagnostické zobrazování chirurgie MeSH
- lidé MeSH
- prospektivní studie MeSH
- trombektomie metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Alberta MeSH
