Validation of a clinical trial composite endpoint for patients with necrotizing soft tissue infections
Validation of a clinical trial composite endpoint for patients with necrotizing soft tissue infections
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DOI：
10.1097/ta.0000000000001564
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发表时间：
2017-10-01
影响因子：
3.4
通讯作者：
Shirvan, Anat
中科院分区：
文献类型：
--
作者：
Bulger, Eileen M.;May, Addison;Shirvan, Anat
目的：我们的目标是建立和验证坏死性软组织感染患者的综合终点，包括局部组织损伤、全身器官功能障碍和死亡率。方法：坏死性感染临床综合终点(NICCE)被定义为：(I)在第28天存活，(Ii)在第14天前有3次或更少的清创，(Iii)首次清创后没有截肢，(Iv)第14天的改良序贯器官衰竭评估评分(MSOFA)。NICCE的成功还与卫生保健资源的利用减少相关，NICCE成功和失败的重症监护病房无病房天数的中位数(四分位数范围)分别为25.3d(21.9-28年)和19.6d(4.325.1)天(单侧Wilcoxon p<；0.001)，无呼吸机天数分别为28(26-28)天和25(14-28)天(p<；0.001)。使用第2期数据集，治疗组(0.5 mg/kg，n=15)显示NICCE成功率为73.3%，而安慰剂组(n=10)为40%。结论：这些数据证明了NICCE终点的成分和表面的内部一致性以及标准的有效性。NICCE为参加坏死性软组织感染临床试验的患者提供了一个展示临床相关治疗效果的机会。版权所有(C)2017 Wolters KluwerHealth，Inc.保留所有权利。
OBJECTIVE: Our objective was to develop and validate a composite endpoint for patients with necrotizing soft tissue infections that incorporates: local tissue injury, systemic organ dysfunction, and mortality.METHODS: The Necrotizing Infection Clinical Composite Endpoint (NICCE) was defined as follows:(i) alive at day 28, (ii) three or less debridements before day 14, (iii) no amputation beyond first debridement, (iv) modified sequential organ failure assessment score score (mSOFA) at day 14 3). NICCE success was also associated with reduced utilization of health care resources, intensive care unit-free days were median (interquartile range) of 25.3 (21.9-28) and 19.6 (4.3-25.1) days (one-sided Wilcoxon p < 0.001) and ventilator-free days were 28 (26-28) versus 25 (14-28) (p < 0.001) for NICCE success versus failure, respectively. Using the phase 2 data set, the treated group (0.5 mg/kg, n = 15) demonstrated a NICCE success rate of 73.3% versus 40% for placebo (n = 10).CONCLUSION: These data demonstrate internal consistency of the components and face and criterion validity of the NICCE endpoint. NICCE offers an opportunity to demonstrate a clinically relevant treatment effect for patients enrolled in clinical trials for necrotizing soft tissue infection. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.