Endovascular Treatment for Acute Large Vessel Occlusion With Ultra-Large Ischemic Core: A Prospective, Multicenter, Randomized, Open-label, Blinded Endpoint Trial (LARGE CORE-MT)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 450
- 试验地点
- 1
- 主要终点
- The primary efficacy endpoint is the mRS score at 90 days after randomization.
研究概览
简要总结
an investigator initiated, prospective, multicenter, randomized, open-label, blinded endpoint trial (PROBE)
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 -
- •Informed consent form was signed.
排除标准
- •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.
研究组 & 干预措施
EVT group
干预措施: Patients assigned to the EVT group should undergo EVT as soon as possible, followed by BMM according to the current EVT guidelines. (Procedure)
Medical group
干预措施: The medical group receives BMM alone. EVT is not performed in the medical group. (Drug)
结局指标
主要结局
The primary efficacy endpoint is the mRS score at 90 days after randomization.
时间窗: at 90 days after randomization.
次要结局
- Infarct volume change from baseline NCCT at 7 (±1) days after randomization or discharge (whichever is earlier), or by MRI at 36 (±12) hours.(at 7 (±1) days after randomization or discharge (whichever is earlier), or by MRI at 36 (±12) hours.)
- EQ-5D-5L score at 90 days.(at 90 days.)
- mRS score at 180 days after randomization.(at 180 days after randomization.)
- Proportion of mRS 0-2 at 90 days and 180 days after randomization.(at 90 days and 180 days after randomization.)
- Proportion of mRS 0-3 at 90 days and 180 days after randomization.(at 90 days and 180 days after randomization.)
- Proportion of early neurological improvement(at day 7 (±1) or discharge (whichever is earlier).)