Endovascular Treatment for Acute Large Vessel Occlusion With Ultra-Large Ischemic Core (LARGE CORE-MT)
Endovascular Treatment for Acute Large Vessel Occlusion With Ultra-Large Ischemic Core: A Prospective, Multicenter, Randomized, Open-label, Blinded Endpoint Trial (LARGE CORE-MT)
Descripción general del estudio
Estado
Descripción detallada
The primary objective is to determine whether EVT combined with BMM, compared with BMM alone, improves functional outcome in patients with intracranial LVO in anterior circulation and ultra large-core treated within 24 hours of symptom onset.
Primary Efficacy Endpoint Analysis The primary efficacy endpoint is the mRS score at 90 days after randomization. The proportional odds assumption will be formally assessed. If this assumption holds (score test p-value > 0.05), the primary effect measure is the common odds ratio (cOR), which will be estimated using an ordinal logistic regression model to assess the shift in the overall distribution of the mRS scale at 90 days. The model will be adjusted for known prognostic factors including baseline ASPECTS score, age, NIHSS score at admission, and intravenous thrombolysis, as well as the randomization stratification factor, i.e., time from stroke onset or last known well to randomization (≤6 hours vs. >6 hours). Unadjusted cOR estimates and confidence intervals (CI) will also be reported. If the assumption is violated, the generalized odds ratio (GenOR) and its 95% CI will be derived as a robust alternative measure of treatment effect.
Secondary Efficacy Endpoints Analysis For the secondary endpoint of mRS score at 180 days after randomization, the same analysis method as for the primary endpoint will be used. For the proportions of mRS 0-2 and mRS 0-3 at 90 days and 180 days, early neurological improvement, a modified Poisson regression model will be used, reporting Risk Ratio and 95% CI, with the same adjustment factors as in the primary endpoint analysis. For the comparison of EQ-5D-5L score at 90 days between two arms, a linear regression model will be used to estimate the mean difference and 95% CI. For the change in infarct volume from baseline assessed by NCCT at 7 (±1) days or discharge (whichever occurs earlier), or by MRI at 36 (±12) hours after randomization, a linear regression model will be used to estimate the mean difference and 95% CI, with treatment group as the study variable and baseline measurement as a covariate; if normality assumptions are violated, the win ratio method will be used.
Safety Analysis For the primary safety endpoint of all-cause mortality within 90 days after randomization, the Chi-squared test or Fisher's exact test will be used for between-group comparison. For the secondary safety endpoints, including incidence of sICH within 24 hours from onset, proportion of early neurological deterioration, procedure- or device-related complications, and serious adverse events adjudicated by the Clinical Events Committee, data summary will be performed by treatment group.
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Guang Zhang, MD, PhD
- Número de teléfono: +86 451 85555099
- Correo electrónico: zhangguang@hrbmu.edu.cn
Ubicaciones de estudio
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Hei Longjiang
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Harbin, Hei Longjiang, Porcelana, 150001
- he First Affiliated Hospital of Harbin Medical University
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Contacto:
- Guang Zhang, M.D., Ph.D.
- Número de teléfono: +86 451 85555099
- Correo electrónico: zhangguang@hrbmu.edu.cn
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Investigador principal:
- Huaizhang SHi, M.D., Ph.D.
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- ≥18 years.
- Symptoms onset or Time last known well ≤ 24 h from randomization.
- Acute ischemic stroke due to an occlusion of the intracranial internal carotid artery, M1 or proximal M2 segment of the middle cerebral artery confirmed by CTA or MRA.
- NCCT or diffusion-weighted imaging (DWI) demonstrating ASPECTS ≤ 2 or infarct core volume (defined as rCBF <30% on CTP) ≥ 100 mL.
- Selection imaging performed ≤ 3 hours before randomization.
- Pre-stroke mRS 0 - 1.
- Informed consent form was signed.
Exclusion Criteria:
- Evidence of intracranial hemorrhage on CT/MRI, including intraparenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, or subdural/epidural hemorrhage.
- Cerebral midline shift or herniation, or other ventricular mass effect with midline shift as confirmed on CT/MRI.
- Bilateral anterior circulation or acute multi-vessel occlusion involving both anterior and posterior circulation, confirmed by CTA or MRA.
- Blood pressure >185/110 mmHg and is refractory to medicine.
- Known coagulopathy, with international normalized ratio (INR) >1.7 or platelet count <100×10⁹/L;
- Current treatment with direct thrombin inhibitors or factor Xa inhibitors;
- Patients with severe organ failure (cardiac, pulmonary, renal, or hepatic);
- Concomitant malignancy or other conditions with life expectancy under 6 months;
- Female who is known to be pregnant;
- Prior endovascular attempt for this stroke;;
- Currently participation in another clinical study;
- Other circumstances that the investigator considers inappropriate for participation.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Único
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: EVT group
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EVT should be performed as soon as possible in patients randomized to the EVT group.
Investigators and clinicians should make every effort to minimize delays related to pre-procedural preparation, with a target interval of no more than 60 minutes from randomization to arterial puncture.
EVT in the EVT group can be performed with any thrombectomy device (NMPA approved) usually used at study site.
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Comparador activo: Medical group
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The administration of medications is at the treating physician's discretion (for example intravenous fibrinolysis, anticoagulants or antiplatelet) according to current AIS management guidelines but may NOT include any intra-arterial therapies.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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The primary efficacy endpoint is the mRS score at 90 days after randomization.
Periodo de tiempo: at 90 days after randomization.
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at 90 days after randomization.
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Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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mRS score at 180 days after randomization.
Periodo de tiempo: at 180 days after randomization.
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at 180 days after randomization.
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Proportion of mRS 0-2 at 90 days and 180 days after randomization.
Periodo de tiempo: at 90 days and 180 days after randomization.
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at 90 days and 180 days after randomization.
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Proportion of mRS 0-3 at 90 days and 180 days after randomization.
Periodo de tiempo: at 90 days and 180 days after randomization.
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at 90 days and 180 days after randomization.
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Proportion of early neurological improvement
Periodo de tiempo: at day 7 (±1) or discharge (whichever is earlier).
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at day 7 (±1) or discharge (whichever is earlier).
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Infarct volume change from baseline NCCT at 7 (±1) days after randomization or discharge (whichever is earlier), or by MRI at 36 (±12) hours.
Periodo de tiempo: at 7 (±1) days after randomization or discharge (whichever is earlier), or by MRI at 36 (±12) hours.
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at 7 (±1) days after randomization or discharge (whichever is earlier), or by MRI at 36 (±12) hours.
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EQ-5D-5L score at 90 days.
Periodo de tiempo: at 90 days.
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at 90 days.
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Otras medidas de resultado
Medida de resultado |
Periodo de tiempo |
|---|---|
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Incidence of all-cause mortality within 90 days after randomization.
Periodo de tiempo: within 90 days after randomization.
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within 90 days after randomization.
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Incidence of symptomatic intracranial hemorrhage (sICH, per Heidelberg Bleeding Classification) at 24±12 hours from onset.
Periodo de tiempo: at 24±12 hours from onset.
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at 24±12 hours from onset.
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Incidence of early neurological deterioration
Periodo de tiempo: defined as a NIHSS increase ≥ 10 points at day 7 (±1) or discharge (whichever is earlier). Death within 7 days of onset is directly judged as neurological deterioration.
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defined as a NIHSS increase ≥ 10 points at day 7 (±1) or discharge (whichever is earlier). Death within 7 days of onset is directly judged as neurological deterioration.
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Procedure- or device-related complications
Periodo de tiempo: perioperative period
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perioperative period
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Serious adverse events (SAE) adjudicated by the Clinical Events Committee.
Periodo de tiempo: within 180 days after randomization
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within 180 days after randomization
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Colaboradores e Investigadores
Investigadores
- Investigador principal: Huaizhang Shi, MD, PhD, The First Affiliated Hospital of Harbin Medical University, China
- Investigador principal: Wei Hu, MD, PhD, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), China
- Investigador principal: Jianmin Liu, MD, PhD, Changhai Hospital, China
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- LARGE CORE-MT
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Marco de tiempo para compartir IPD
Criterios de acceso compartido de IPD
- The data sharing will be only for the purposes of health and medical research and within the constraints of the consent under which the data were originally gathered.
- The Custodian of the Collection will not consider any Proposals for data sharing that unblind, or potentially unblind, randomised comparisons in active / ongoing trials.
- Requesters should be employees of a recognised academic institution, health service organisation, commercial research organisation or from the pharmaceutical industry. Requesters must have experience in medical research.
- Requesters must be able to demonstrate through their peer review publications in the area of interest their ability to carry out the proposed use of the requested dataset from a Collection.
- The Requesters must not have a conflict of interest that may potentially influence their interpretation of any analyses.
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
Información sobre medicamentos y dispositivos, documentos del estudio
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