Meng Xia, Li Shuya, Dai Hongguo, Lu Guozhi, Wang Weiwei, Che Fengyuan, Geng Yu, Sun Minghui, Li Xiyan, Li Hao, Wang Yongjun
China National Clinical Research Center for Neurological Diseases, Beijing.
Departments of Neurology and Clinical Trial Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
JAMA. 2024 Nov 5;332(17):1437-1445. doi: 10.1001/jama.2024.14721.
Tenecteplase is a bioengineered variant of alteplase with greater fibrin specificity and a longer half-life, allowing single-bolus administration. Evidence on the treatment effect of tenecteplase 0.25 mg/kg in Chinese patients with acute ischemic stroke (AIS) is limited.
To establish the noninferiority of tenecteplase to alteplase in patients with AIS within 4.5 hours of symptom onset.
DESIGN, SETTING, AND PARTICIPANTS: The ORIGINAL study was a multicenter, active-controlled, parallel-group, randomized, open-label, blinded end point, noninferiority trial conducted between July 14, 2021, and July 14, 2023. Participants were recruited from 55 neurology clinics and stroke centers in China and were eligible if they had AIS with a National Institutes of Health Stroke Scale score of 1 to 25 with measurable neurologic deficit and were symptomatic for at least 30 minutes without significant improvement.
Patients were randomized (1:1) within 4.5 hours of symptom onset to receive intravenous tenecteplase (0.25 mg/kg) or intravenous alteplase (0.9 mg/kg).
The primary outcome was the proportion of patients with a modified Rankin Scale (mRS) score of 0 or 1 (no symptoms or no significant disability) at day 90, tested for noninferiority (risk ratio [RR] margin, 0.937). Safety end points included symptomatic intracerebral hemorrhage (per European Cooperative Acute Stroke Study III definition) and 90-day all-cause mortality.
Among the 1489 patients randomized, 1465 patients were included in the full analysis set (732 in the tenecteplase group; 733 in the alteplase group) and 446 (30.4%) were female. The primary outcome occurred in 72.7% (532/732) of patients receiving tenecteplase and 70.3% (515/733) receiving alteplase (RR, 1.03 [95% CI, 0.97-1.09]; noninferiority threshold met). Symptomatic intracerebral hemorrhage occurred in 9 patients (1.2%) in each group (RR, 1.01 [95% CI, 0.37-2.70]). The 90-day mortality rate was 4.6% (34/732) in the tenecteplase group and 5.8% (43/736) in the alteplase group (RR, 0.80 [95% CI, 0.51-1.23]).
In patients with AIS eligible for intravenous thrombolysis within 4.5 hours after stroke onset, tenecteplase was noninferior to alteplase with respect to excellent functional outcome (mRS score of 0 or 1) at 90 days and had a similar safety profile. Findings from this study support tenecteplase as a suitable alternative to alteplase in this setting.
ClinicalTrials.gov Identifier: NCT04915729.
替奈普酶是阿替普酶的一种生物工程变体，具有更高的纤维蛋白特异性和更长的半衰期，允许单次静脉推注给药。关于替奈普酶0.25mg/kg治疗中国急性缺血性卒中（AIS）患者的疗效证据有限。
确定症状发作4.5小时内AIS患者中替奈普酶不劣于阿替普酶。
设计、设置和参与者：ORIGINAL研究是一项多中心、活性药物对照、平行组、随机、开放标签、盲法终点、非劣效性试验，于2021年7月14日至2023年7月14日进行。参与者从中国55家神经内科诊所和卒中中心招募，入选标准为患有AIS、美国国立卫生研究院卒中量表评分为1至25分、有可测量的神经功能缺损、症状持续至少30分钟且无明显改善。
患者在症状发作4.5小时内随机（1:1）接受静脉注射替奈普酶（0.25mg/kg）或静脉注射阿替普酶（0.9mg/kg）。
主要结局是90天时改良Rankin量表（mRS）评分为0或1（无症状或无明显残疾）的患者比例，进行非劣效性检验（风险比[RR]界值，0.937）。安全性终点包括症状性脑出血（根据欧洲急性卒中协作研究III定义）和90天全因死亡率。
在1489例随机分组的患者中，1465例患者纳入全分析集（替奈普酶组732例；阿替普酶组733例），446例（30.4%）为女性。接受替奈普酶治疗的患者中主要结局发生率为72.7%（532/732），接受阿替普酶治疗的患者中为70.3%（515/733）（RR，1.03[95%CI，0.97 - 1.09]；达到非劣效性界值）。每组有9例患者（1.2%）发生症状性脑出血（RR，1.01[95%CI，0.37 - 2.70]）。替奈普酶组90天死亡率为4.6%（34/732），阿替普酶组为5.8%（43/736）（RR，0.80[95%CI，0.51 - 1.23]）。
对于卒中发作后4.5小时内符合静脉溶栓条件的AIS患者，替奈普酶在90天时的良好功能结局（mRS评分为0或1）方面不劣于阿替普酶，且安全性相似。本研究结果支持替奈普酶在此情况下作为阿替普酶的合适替代药物。
ClinicalTrials.gov标识符：NCT04915729。
