ImportanceThe effect of argatroban in patients with acute ischemic stroke (AIS) and early neurological deterioration (END) is unknown.ObjectiveTo assess the efficacy of argatroban for END in AIS.Design, Setting, and ParticipantsThis open-label, blinded–end point, randomized clinical trial was conducted from April 4, 2020, through July 31, 2022. The date of final follow-up was October 31, 2022. This was a multicenter trial. Eligible patients were adults with AIS who experienced END, which was defined as an increase of 2 or more points on the National Institutes of Health Stroke Scale within 48 hours from symptom onset. Patients who withdrew consent, experienced duplicate randomization, or were lost to follow-up were excluded from the study.InterventionsPatients were randomly assigned to the argatroban group and control group within 48 hours of symptom onset. Both groups received standard therapy based on guidelines, including oral mono or dual antiplatelet therapy. The argatroban group received intravenous argatroban for 7 days (continuous infusion at a dose of 60 mg per day for 2 days, followed by 20 mg per day for 5 days) in addition to standard therapy.Main Outcome and MeasureThe primary end point was good functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 3.ResultsA total of 628 patients (mean [SD] age, 65 [11.9] years; 400 male [63.7%]) were included in this study (argatroban group, 314 [50%] and control group, 314 [50%]). Of these, 18 withdrew consent, 1 had duplicate randomization, and 8 were lost to follow-up. A total of 601 patients with stroke were included in the intention-to-treat analysis. Finally, 564 patients were included in the per-protocol analysis as 6 participants in the argatroban group and 31 participants in the control group did not follow the complete protocol. The number of patients with good functional outcome at 90 days was 240 (80.5%) in the argatroban group and 222 (73.3%) in the control group (risk difference, 7.2%; 95% CI, 0.6%-14.0%; risk ratio, 1.10; 95% CI, 1.01-1.20; P = .04). The proportion of symptomatic intracranial hemorrhage was 3 of 317 (0.9%) in the argatroban group and 2 of 272 (0.7%) in the control group (P = .78).Conclusions and RelevanceAmong patients with AIS with END, treatment with argatroban and antiplatelet therapy resulted in a better functional outcome at 90 days. This trial provided evidence to support the use of argatroban in reducing disability for patients with END.Trial RegistrationClinicalTrials.gov Identifier: NCT04275180

中文翻译：

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阿加曲班治疗伴有早期神经功能恶化的急性缺血性中风患者

重要性阿加曲班对急性缺血性卒中 (AIS) 和早期神经功能恶化 (END) 患者的影响尚不清楚。目的评估阿加曲班对 AIS 中 END 的疗效。设计、设置和参与者此开放标签、盲法终点、随机临床试验于2020年4月4日至2022年7月31日进行。最终随访日期为2022年10月31日。这是一项多中心试验。符合条件的患者是患有 END 的 AIS 成人患者，END 定义为美国国立卫生研究院卒中量表在症状出现后 48 小时内增加 2 分或更多分。撤回同意、经历重复随机分组或失访的患者被排除在研究之外。干预措施患者在症状出现 48 小时内被随机分配到阿加曲班组和对照组。两组均接受基于指南的标准治疗，包括口服单药或双联抗血小板治疗。阿加曲班组在标准治疗的基础上接受静脉注射阿加曲班 7 天（以每天 60 mg 的剂量连续输注 2 天，随后每天 20 mg 连续输注 5 天）。 主要结果和措施 主要终点是良好的功能90 天的结果，定义为 0 至 3 的改良 Rankin 量表评分。 结果 本研究共纳入 628 名患者（平均 [SD] 年龄，65 [11.9] 岁；400 名男性 [63.7%]）（阿加曲班组） ，314 [50%] 和对照组，314 [50%]）。其中，18 人撤回同意，1 人进行重复随机分组，8 人失访。意向治疗分析共纳入 601 名中风患者。最后，564 名患者被纳入符合方案分析，因为阿加曲班组有 6 名参与者，对照组有 31 名参与者没有遵循完整的方案。90 天时功能结果良好的患者人数，阿加曲班组为 240 例（80.5%），对照组为 222 例（73.3%）（风险差异，7.2%；95% CI，0.6%-14.0%；风险比，1.10；95% CI，1.01-1.20；磷= .04)。阿加曲班组有症状性颅内出血的比例为 317 例中的 3 例（0.9%），对照组为 272 例中的 2 例（0.7%）。磷= .78)。结论和相关性在患有 END 的 AIS 患者中，阿加曲班和抗血小板治疗在 90 天时产生了更好的功能结果。该试验提供了证据支持使用阿加曲班来减少 END 患者的残疾。试验注册ClinicalTrials.gov 标识符：NCT04275180