Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial.

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. 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. Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial. 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. 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. 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. ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31

Trombosis aguda de la arteria basilar

Resumen: La trombosis aguda de la arteria basilar (TAB) ha sido considerada una catástrofe neurológica. Únicamente alrededor de un 20% de los pacientes alcanza un buen pronóstico con tratamiento convencional. Es importante establecer una sospecha diagnóstica precoz para evitar un retraso en el inicio del tratamiento. La evaluación diagnóstica incluye confirmación de la oclusión basilar y estimación de la viabilidad del tejido isquémico, y puede realizarse con resonancia magnética multiparamétrica o con angiotomografía computarizada combinada con sus imágenes fuente. La recanalización arterial precoz determina la posibilidad de alcanzar un buen pronóstico; sin embargo, se desconoce cuál es el mejor tratamiento de la TAB. No se ha demostrado que la trombólisis intraarterial sea superior a la intravenosa, de modo que en ausencia de contraindicaciones debe iniciarse cuanto antes la trombólisis intravenosa, que puede ser el tratamiento principal si no se cuenta con acceso al neurointervencionismo. Recientemente se han notificado tasas excelentes de buen pronóstico (50% de independencia funcional) empleando estrategias escalonadas de combinación de varias modalidades terapéuticas (trombólisis intravenosa ultraprecoz seguida de trombectomía mecánica endovascular de rescate). Estos resultados representan una esperanza para pacientes y neurólogos y suponen un reclamo para continuar innovando e investigando en este campo. Abstract: Acute basilar artery thrombosis (ABT) has been largely considered a neurological catastrophe. With conventional treatment, only around 20% of patients achieve functional independence. An early presumptive diagnosis is essential to avoid treatment delay. Either multiparametric magnetic resonance imaging or computed tomography angiography source images may represent valid non-invasive tools to confirm ABT and evaluate ischemic tissue viability.The main determinant of ABT outcome is early recanalization but the most effective therapeutic option remains to be clarified. The BASICS prospective registry showed no superiority of intra-arterial over intravenous thrombolysis. Therefore, in the absence of contraindications, intravenous thrombolysis should be started as soon as possible and can be used as the main therapy when interventional procedures are not available. However, recent case series have reported high rates of functional independence (50%) after staged escalation therapy (ultra-early intravenous thrombolysis followed by on-demand endovascular mechanical thrombectomy). These results represent a hope for patients and neurologists and reinforce the need for innovation and research in this field. Palabras clave: Ictus, Pronóstico, Trombosis basilar, Cuidados neurocríticos, Keywords: Stroke, Outcome, Basilar thrombosis, Neurocritical car