Safety and efficacy of nerinetide in patients with acute ischaemic stroke enrolled in the early window: a post-hoc meta-analysis of individual patient data from three randomised trials.

However, none of the trials faithfully replicated the inclusion criteria of the animal studies that provided the rationale for the clinical trials-ie, treatment within 3 h of stroke onset and selected for reperfusion without previous thrombolysis.

然而，这些试验中没有一个能够忠实地复制出为临床试验提供理论依据的动物研究的纳入标准——即在中风发作后3小时内进行治疗，并选择在没有先前溶栓的情况下进行再灌注。

We aimed to investigate whether a clinical benefit of nerinetide might be seen in the subgroup of patients enrolled in these three clinical trials who met the criteria used in the animal studies.

我们的目标是研究在这些三项临床试验中符合动物研究标准的患者亚组中，nerinetide是否可能显示出临床益处。

Methods

In this post-hoc individual patient data meta-analysis, we pooled data from the ESCAPE-NA1, ESCAPE-NEXT, and FRONTIER trials, which were done at 135 stroke centres in 13 countries (Canada, Australia, Germany, Ireland, Italy, the Netherlands, Norway, Singapore, South Korea, Sweden, Switzerland, the UK, and the USA).

在这项事后个体患者数据荟萃分析中，我们合并了ESCAPE-NA1、ESCAPE-NEXT和FRONTIER试验的数据，这些试验在13个国家的135个卒中中心进行（加拿大、澳大利亚、德国、爱尔兰、意大利、荷兰、挪威、新加坡、韩国、瑞典、瑞士、英国和美国）。

We included all participants who were enrolled within 3 h of acute ischaemic stroke onset, treated with study drug (nerinetide or placebo; randomised 1:1), and selected for reperfusion with thrombolysis, endovascular thrombectomy, or both.

我们纳入了所有在急性缺血性中风发作后3小时内入组的参与者，他们接受了研究药物（nerinetide或安慰剂；随机分配比例为1:1），并选择接受溶栓、血管内血栓切除术或两者联合治疗。

The primary endpoint was the number of responders at day 90, which was defined as people with a favourable outcome as per the primary endpoint prespecified in their respective trial. The primary endpoint was analysed by logistic regression, adjusted for age, stroke severity, and trial.

主要终点是第90天的反应者数量，这被定义为根据各自试验预先设定的主要终点具有有利结果的人。主要终点通过逻辑回归进行分析，根据年龄、中风严重程度和试验进行了调整。

Results

Between March 26, 2015, and Jan 31, 2023, 2487 participants were enrolled in the three trials, of whom 690 met criteria for this pooled analysis (389 participants in the nerinetide group and 301 participants in the placebo group). 364 (53%) of 690 participants were men and 326 (47%) were women.

在2015年3月26日至2023年1月31日期间，共有2487名参与者参与了三项试验，其中690人符合本次汇总分析的标准（nerinetide组389人，安慰剂组301人）。690名参与者中，364人（53%）为男性，326人（47%）为女性。

The median age of participants was 76 years (IQR 66-83) and median baseline National Institutes of Health Stroke Scale score was 17 (11-21). 216 (56%) of 389 participants were responders at day 90 in the nerinetide group compared with 144 (48%) of 301 in the placebo group (adjusted odds ratio [aOR] 1·48, 95% CI 1·07-2·06; p=0·017). 62 (16%) of 389 people in the nerinetide group died compared with 55 (18%) of 301 people in the placebo group (aOR 0·81, 95% CI 0·53-1·24; p=0·34).

参与者的中位年龄为76岁（四分位数间距66-83岁），基线时的美国国立卫生研究院卒中量表评分为17（11-21）。在nerinetide组中，90天时有216人（56%）为应答者，而在安慰剂组中，有144人（48%）为应答者（调整后优势比[aOR] 1·48，95%置信区间[CI] 1·07-2·06；p=0·017）。nerinetide组中有62人（16%）死亡，而安慰剂组中有55人（18%）死亡（aOR 0·81，95% CI 0·53-1·24；p=0·34）。

No safety concerns were identified in either group.

在两组中均未发现安全问题。

interpretation

Nerinetide showed a clinically significant benefit over several outcome measures, including the modified Rankin Scale score, the incidenceof stroke worsening, and infarction volumes.

Nerinetide在包括改良Rankin量表评分、中风恶化发生率和梗死体积在内的多个结果指标上显示出临床意义显著的益处。

Neuroprotection with nerinetide might, therefore, be indicated for patients within 3 h of stroke onset and who are selected for reperfusion.

因此，对于发病3小时内并选择进行再灌注的患者，使用nerinetide进行神经保护可能是有益的。

These inclusion criteria should be tested in a future trial.

这些纳入标准应在未来的试验中进行测试。

funding

None.

无。