Yoo Albert J, Zaidat Osama O, Sheth Sunil A, Rai Ansaar T, Ortega-Gutierrez Santiago, Given Curtis A, Zaidi Syed F, Grandhi Ramesh, Cuellar Hugo, Mokin Maxim, Katz Jeffrey M, Alshekhlee Amer, Taqi Muhammad A, Ansari Sameer A, Siddiqui Adnan H, Barazangi Nobl, English Joey D, Maud Alberto, Kirmani Jawad, Gupta Rishi, Yavagal Dileep R, Tarpley Jason, Pandya Dhruvil J, Cress Marshall C, Dharmadhikari Sushrut, Asif Kaiz S, Kass-Hout Tareq, Puri Ajit S, Janjua Nazli, Majjhoo Aniel Q, Badruddin Aamir, Edgell Randall C, Khatri Rakesh, Morgan Larry, Razak Anmar, Zha Alicia, Khandelwal Priyank, Mueller-Kronast Nils, Rivet Dennis J, Wolfe Thomas, Snelling Brian, Sultan-Qurraie Ali, Lin Shao-Pow, Khangura Rajkamal, Spiotta Alejandro M, Bhuva Parita, Salazar-Marioni Sergio, Lin Eugene, Tarabishy Abdul R, Samaniego Edgar A, Kolikonda Murali K, Jumaa Mouhammad A, Reddy Vivek K, Sharma Pankaj, Berkhemer Olvert A, van Doormaal Pieter-Jan, van Es Adriaan C G M, van Zwam Wim H, Emmer Bart J, Beenen Ludo F, Majoie Charles B L M, Buderer Nancy, Detry Michelle A, Bosse Anna, Graves Todd L, Saunders Christina, Elijovich Lucas, Jadhav Ashutosh, Patterson Mary, Slight Hannah, Below Kristine, Al Kasab Sami
Division of Neurointervention, Texas Stroke Institute, Dallas-Fort Worth.
Bon Secours Mercy Health Neuroscience Institute, Toledo, Ohio.
JAMA. 2024 Sep 23;332(16):1355-66. doi: 10.1001/jama.2024.13933.
Recent large infarct thrombectomy trials used heterogeneous imaging modalities and time windows for patient selection. Noncontrast computed tomographic (CT) scan is the most common stroke imaging approach. It remains uncertain whether thrombectomy is effective for patients with large infarcts identified using noncontrast CT alone within 24 hours of stroke onset.
To evaluate the effect of thrombectomy in patients with a large infarct on a noncontrast CT scan within 24 hours of onset.
DESIGN, SETTING, AND PARTICIPANTS: Open-label, blinded-end point, bayesian-adaptive randomized trial with interim analyses for early stopping (futility or success) or population enrichment, which was conducted at 47 US academic and community-based stroke thrombectomy centers. Three hundred patients presenting within 24 hours with anterior-circulation, large-vessel occlusion and large infarct on noncontrast CT scan, with Alberta Stroke Program Early CT Scores of 2 to 5, were randomized to undergo thrombectomy or usual care. Enrollment occurred July 16, 2019 to October 17, 2022; final follow-up, January 25, 2023.
The intervention patients (n = 152) underwent endovascular treatment using standard thrombectomy devices and usual medical care. Control patients (n = 148) underwent usual medical care alone.
The primary efficacy end point was improvement in 90-day functional outcome measured using mean utility-weighted modified Rankin Scale (UW-mRS) scores (range, 0 [death or severe disability] to 10 [no symptoms]; minimum clinically important difference, 0.3). A bayesian model determined the posterior probability that the intervention would be superior to usual care; statistical significance was a 1-sided posterior probability of .975 or more. The primary adverse event end point was 90-day mortality; secondary adverse event end points included symptomatic intracranial hemorrhage and radiographic intracranial hemorrhage.
The trial enrolled 300 patients (152 intervention, 148 control; 138 females [46%]; median age, 67 years), without early stopping or enrichment; 297 patients completed the 90-day follow-up. The mean (SD) 90-day UW-mRS score was 2.93 (3.39) for the intervention group vs 2.27 (2.98) for the control group with an adjusted difference of 0.63 (95% credible interval [CrI], -0.09 to 1.34; posterior probability for superiority of thrombectomy, .96). The 90-day mortality was similar between groups: 35.3% (53 of 150) for the intervention group vs 33.3% (49 of 147) for the control group. Six of 151 patients (4.0%) in the intervention group and 2 of 149 (1.3%) in the control group experienced 24-hour symptomatic intracranial hemorrhage. Fourteen patients of 148 (9.5%) in the intervention group vs 4 of 146 (2.7%) in the control group experienced parenchymal hematoma type 1 hemorrhages; 14 (9.5%) in the intervention group vs 5 (3.4%) in the control group experienced parenchymal hematoma type 2 hemorrhages; and 24 (16.2%) in the intervention group vs 9 (6.2%) in the control group experienced subarachnoid hemorrhages.
Among patients with a large infarct on noncontrast CT within 24 hours, thrombectomy did not demonstrate improvement in functional outcomes. But the width of the credible interval around the effect estimate includes the possibility of both no important effect and a clinically relevant benefit, so the potential role of thrombectomy with this imaging approach and time window will likely require additional study.
ClinicalTrials.gov Identifier: NCT03805308.
近期大型梗死灶血栓切除术试验在患者选择方面采用了异质的成像方式和时间窗。非增强计算机断层扫描（CT）是最常见的卒中成像方法。对于在卒中发病24小时内仅通过非增强CT识别出的大型梗死灶患者，血栓切除术是否有效仍不确定。
评估发病24小时内非增强CT显示有大型梗死灶的患者接受血栓切除术的效果。
设计、地点和参与者：开放标签、盲终点、贝叶斯适应性随机试验，进行中期分析以提前终止试验（无效或成功）或进行人群富集，该试验在美国47个学术和社区卒中血栓切除术中心开展。300例在24小时内出现前循环大血管闭塞且非增强CT显示有大型梗死灶、阿尔伯塔卒中项目早期CT评分2至5分的患者被随机分组，分别接受血栓切除术或常规治疗。入组时间为2019年7月16日至2022年10月17日；最终随访时间为2023年1月25日。
干预组患者（n = 152）使用标准血栓切除装置进行血管内治疗并接受常规医疗护理。对照组患者（n = 148）仅接受常规医疗护理。
主要疗效终点是使用平均效用加权改良Rankin量表（UW - mRS）评分（范围为0[死亡或严重残疾]至10[无症状]；最小临床重要差异为0.3）评估的90天功能结局改善情况。贝叶斯模型确定干预优于常规治疗的后验概率；统计学显著性为单侧后验概率≥0.975。主要不良事件终点是90天死亡率；次要不良事件终点包括症状性颅内出血和影像学颅内出血。
该试验纳入300例患者（152例干预组，148例对照组；138例女性[46%]；中位年龄67岁），未提前终止试验或进行人群富集；297例患者完成90天随访。干预组90天UW - mRS评分的均值（标准差）为2.93（3.39），对照组为2.27（2.98），调整后差异为0.63（95%可信区间[CrI]，-0.09至1.34；血栓切除术优越性的后验概率为0.96）。两组90天死亡率相似：干预组为35.3%（150例中的53例），对照组为33.3%（147例中的49例）。干预组151例患者中有6例（4.0%）发生24小时症状性颅内出血，对照组149例中有2例（1. 3%）。干预组148例患者中有14例（9.5%）发生1型实质性血肿，对照组146例中有4例（2.7%）；干预组14例（9.5%）发生2型实质性血肿，对照组5例（3.4%）；干预组24例（16.2%）发生蛛网膜下腔出血，对照组9例（6.2%）。
在发病24小时内非增强CT显示有大型梗死灶的患者中，血栓切除术未显示功能结局改善。但效应估计值可信区间的宽度包括无重要效应和有临床相关益处两种可能性，因此这种成像方法和时间窗下血栓切除术的潜在作用可能需要进一步研究。
ClinicalTrials.gov标识符：NCT03805308。
