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)
Visão geral do estudo
Status
Descrição detalhada
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 estudo
Inscrição (Estimado)
Estágio
- Não aplicável
Contactos e Locais
Contato de estudo
- Nome: Guang Zhang, MD, PhD
- Número de telefone: +86 451 85555099
- E-mail: zhangguang@hrbmu.edu.cn
Locais de estudo
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Hei Longjiang
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Harbin, Hei Longjiang, China, 150001
- he First Affiliated Hospital of Harbin Medical University
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Contato:
- Guang Zhang, M.D., Ph.D.
- Número de telefone: +86 451 85555099
- E-mail: zhangguang@hrbmu.edu.cn
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Investigador principal:
- Huaizhang SHi, M.D., Ph.D.
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
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.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Solteiro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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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 Ativo: 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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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
|---|---|
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The primary efficacy endpoint is the mRS score at 90 days after randomization.
Prazo: at 90 days after randomization.
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at 90 days after randomization.
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Medidas de resultados secundários
Medida de resultado |
Prazo |
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mRS score at 180 days after randomization.
Prazo: 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.
Prazo: 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.
Prazo: 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
Prazo: 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.
Prazo: 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.
Prazo: at 90 days.
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at 90 days.
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Outras medidas de resultado
Medida de resultado |
Prazo |
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Incidence of all-cause mortality within 90 days after randomization.
Prazo: 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.
Prazo: 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
Prazo: 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
Prazo: perioperative period
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perioperative period
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Serious adverse events (SAE) adjudicated by the Clinical Events Committee.
Prazo: 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
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- LARGE CORE-MT
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Prazo de Compartilhamento de IPD
Critérios de acesso de compartilhamento 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 informação de suporte de compartilhamento de IPD
- PROTOCOLO DE ESTUDO
- SEIVA
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