Randomized, Multicenter Trial of ARTSS-2 (Argatroban With Recombinant Tissue Plasminogen Activator for Acute Stroke).
Randomized, Multicenter Trial of ARTSS-2 (Argatroban With Recombinant Tissue Plasminogen Activator for Acute Stroke).
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DOI：
10.1161/strokeaha.117.016720
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发表时间：
2017-06
期刊：
影响因子：
8.3
通讯作者：
ARTSS-2 Investigators
中科院分区：
文献类型：
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作者：
Barreto AD;Ford GA;Shen L;Pedroza C;Tyson J;Cai C;Rahbar MH;Grotta JC;ARTSS-2 Investigators
我们进行了一项随机探索性研究，以评估辅助阿加曲班（一种直接凝血酶抑制剂）用于rt-PA治疗的缺血性卒中患者的安全性和良好结果的可能性。接受标准剂量rt-PA治疗的患者，未接受血管内治疗，随机分为不接受阿加曲班或阿加曲班（100 μg/kg），随后输注1 μg/kg/min（低剂量）或3 μg/kg/min（高剂量），持续48小时。安全性是症状性脑出血（siich）的发生率。使用保守贝叶斯泊松模型估计临床获益概率（90天mRS 0-1）（以相对风险为中心的中性先验概率[RR]=1.0, 95%先验区间：0.33-3.0）。90例患者随机分组：29例患者单独接受rt-PA治疗，30例接受rt-PA +低剂量阿加曲班治疗，31例接受rt-PA +高剂量阿加曲班治疗。对照组、低剂量组和高剂量组siich发生率相似：3/29 (10%)；4/30 (13%);和2/31（7%）。在第90天，6 (21%)rt-PA单独；低剂量9例（30%），高剂量10例（32%），mRS 0-1。低剂量、高剂量和低剂量或高剂量的mRS 0-1的RR（95%可信区间）分别为1.17（0.57,2.37）、1.27（0.63,2.53）和1.34（0.68,2.76）。辅助阿加曲班在低剂量、高剂量和低剂量或高剂量下优于单独rt-PA的概率分别为67%、74%和79%。在接受rt-PA治疗的患者中，辅助阿加曲班与sICH风险增加无关，并提供了明确有效性试验的证据。
We conducted a randomized exploratory study to assess safety and the probability of a favorable outcome with adjunctive argatroban, a direct thrombin-inhibitor, administered to rt-PA treated ischemic stroke patients. Patients treated with standard-dose rt-PA, not receiving endovascular therapy, were randomized to receive no argatroban or argatroban (100-μg/kg bolus) followed by infusion of either 1 μg/kg/min (low-dose) or 3 μg/kg/min (high-dose) for 48 hours. Safety was incidence of symptomatic intracerebral hemorrhage (sICH). Probability of clinical benefit (mRS 0–1 at 90-days) was estimated using a conservative Bayesian Poisson model (neutral prior probability centered at relative risk [RR]=1.0 and 95% prior intervals: 0.33–3.0). Ninety patients were randomized: 29 to rt-PA alone, 30 to rt-PA + low-dose argatroban, and 31 to rt-PA + high-dose argatroban. Rates of sICH were similar among control, low-dose and high-dose arms: 3/29 (10%); 4/30 (13%); and 2/31 (7%), respectively. At 90-days 6 (21%) rt-PA alone; 9 (30%) low-dose, and 10 (32%) high-dose patients were mRS 0–1. The RR (95% Credible Interval) for mRS 0–1 with low, high, and either low or high dose argatroban was 1.17 (0.57, 2.37), 1.27 (0.63, 2.53), and 1.34 (0.68, 2.76). The probability that adjunctive argatroban was superior to rt-PA alone was 67%, 74%, and 79% for low, high, and low or high dose, respectively. In patients treated with rt-PA, adjunctive argatroban was not associated with increased risk of sICH and provides evidence that a definitive effectiveness trial is indicated.