文章：

阿司匹林治疗原发性血小板增多症（ARES）II期随机试验设计：将血清血栓素B2检测作为临床环境中不同阿司匹林给药方案评估工具的实施

The Aspirin Regimens in Essential Thrombocythemia (ARES) phase II randomized trial design: Implementation of the serum thromboxane B2 assay as an evaluation tool of different aspirin dosing regimens in the clinical setting

原文发布日期：2018-06-01

DOI: 10.1038/s41408-018-0078-3

类型: Article

开放获取: 是

英文摘要：

Once-daily (od), low-dose aspirin (75–100 mg) is recommended to reduce the thrombotic risk of patients with essential thrombocytemia (ET). This practice is based on data extrapolated from other high-risk patients and an aspirin trial in polycythemia vera, with the assumption of similar aspirin pharmacodynamics in the two settings. However, the pharmacodynamics of low-dose aspirin is impaired in ET, reflecting accelerated renewal of platelet cyclooxygenase (COX)-1. ARES is a parallel-arm, placebo-controlled, randomized, dose-finding, phase II trial enrolling 300 ET patients to address two main questions. First, whether twice or three times 100 mg aspirin daily dosing is superior to the standard od regimen in inhibiting platelet thromboxane (TX)A2 production, without inhibiting vascular prostacyclin biosynthesis. Second, whether long-term persistence of superior biochemical efficacy can be safely maintained with multiple vs. single dosing aspirin regimen. Considering that the primary study end point is serum TXB2, a surrogate biomarker of clinical efficacy, a preliminary exercise of reproducibility and validation of this biomarker across all the 11 participating centers was implemented. The results of this preliminary phase demonstrate the importance of controlling reproducibility of biomarkers in multicenter trials and the feasibility of using serum TXB2 as a reliable end point for dose-finding studies of novel aspirin regimens.

摘要翻译： 

建议每日一次（od）服用低剂量阿司匹林（75-100毫克）以降低原发性血小板增多症（ET）患者的血栓风险。该实践基于从其他高危患者群体中 extrapolated 的数据以及在真性红细胞增多症中进行的一项阿司匹林试验结果，其前提是假设两种情况下阿司匹林的药效学相似。然而，在ET患者中，低剂量阿司匹林的药效学会受损，这反映了血小板环氧化酶（COX）-1的加速更新。ARES试验是一项平行组、安慰剂对照、随机、剂量探索的II期试验，共纳入300例ET患者，旨在解决两个主要问题：首先，在抑制血小板血栓素（TX）A2产生方面，每日两次或三次100毫克阿司匹林给药方案是否优于标准每日一次方案，同时不抑制血管前列腺素的生物合成；其次，与单次给药方案相比，多次给药阿司匹林方案能否在长期内安全维持更优的生化疗效。考虑到主要研究终点是临床疗效的替代生物标志物——血清TXB2，我们在所有11个参与中心进行了一项关于该生物标志物可重复性和验证的初步实践。这一初步阶段的结果表明，在多中心试验中控制生物标志物可重复性的重要性，以及使用血清TXB2作为新型阿司匹林方案剂量探索研究的可靠终点的可行性。

原文链接：

The Aspirin Regimens in Essential Thrombocythemia (ARES) phase II randomized trial design: Implementation of the serum thromboxane B2 assay as an evaluation tool of different aspirin dosing regimens in the clinical setting