Clinical trial endpoints in acute kidney injury.
Clinical trial endpoints in acute kidney injury.
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急性肾脏损伤的临床试验终点。
DOI：
10.1159/000363725
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Shaw AD
中科院分区：
文献类型：
--
作者：
Billings FT 4th;Shaw AD
急性肾损伤（AKI）诊断的共识标准的发展和使用，以及最近确定的肾实质损伤标志物作为临床试验终点的纳入，提高了医生在不同患者群体中比较AKI发病率和严重程度的能力，为测试新疗法提供了靶点，并可能增加对AKI机制的了解。到目前为止，这些标记还没有一致地转化为重要的临床结果。这是因为这些肾脏损伤/功能障碍的标志是护理过程的测量（而不是肾功能持续受损的指示），还是因为患者确实从AKI中康复了？医生目前测量肾功能储备的能力有限，AKI病例对长期发病率的最终后果仍不清楚。毫无疑问，发生AKI的患者比未发生AKI的患者预后更差，但研究人员现在意识到在AKI临床试验中所有受试者中测量有临床意义的肾脏终点的价值。这些结局的重要例子包括持续的肾功能受损，新的血液透析和死亡。我们建议将这些主要肾脏不良事件（MAKE）纳入所有有效性临床试验。在AKI后30,60或90天评估MAKE组合的适应性（即MAKE30或MAKE90）将提高我们理解和治疗AKI的能力，也可能提供一个共识组合，以便比较不同的干预措施。另一方面，I期和II期临床试验的主要终点应该继续使用肾损伤/功能障碍的连续标记以及“硬”临床结果，以便在有限的受试者暴露于未经测试的治疗的情况下产生有意义的数据。通过这样做，研究人员可以在不需要大样本量的情况下评估安全性，证明未知治疗的治疗效果，并为后续研究提供动力。相比之下，III期试验应包括共识AKI标准和更重要的后续临床结果，如MAKE90，作为主要终点。
The development and use of consensus criteria for acute kidney injury (AKI) diagnosis and the inclusion of recently identified markers of renal parenchymal damage as endpoints in clinical trials have improved the ability of physicians to compare the incidence and severity of AKI across patient populations, provided targets for testing new treatments, and may increase insight into the mechanisms of AKI. To date, these markers have not consistently translated into important clinical outcomes. Is that because these markers of renal injury/dysfunction are measurements of process of care (and not indicative of persistently impaired renal function), or is it because patients do actually recover from AKI? Physicians currently have limited ability to measure renal function reserve, and the ultimate consequence of a case of AKI on long-term morbidity remains unclear. There is little doubt that groups of patients who develop AKI have worse outcomes than groups of patients who do not, but investigators are now realizing the value of measuring clinically meaningful renal endpoints in all subjects enrolled in AKI clinical trials. Important examples of these outcomes include persistently impaired renal function, new hemodialysis, and death. We propose that these major adverse kidney events (MAKE) be included in all effectiveness clinical trials. Adaptation of the MAKE composite assessed 30, 60, or 90 days following AKI (i.e., MAKE30 or MAKE90) will improve our capacity to understand and treat AKI and may also provide a consensus composite to allow comparison of different interventions. Primary endpoints for phase I and II clinical trials, on the other hand, should continue to use continuous markers of renal injury/dysfunction as well as ‘hard’ clinical outcomes in order to generate meaningful data with limited subject exposure to untested treatments. By doing so, investigators may assess safety without requiring large sample sizes, demonstrate treatment effect of an unknown therapeutic, and power subsequent studies. In contrast, phase III trials should include consensus AKI criteria and more important subsequent clinical outcomes, such as MAKE90, as primary endpoints.
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DOI：
10.1097/01.asn.0000079042.13465.1a
发表时间：
2003-08-01
影响因子：
13.6
作者：
Mehta, RL;Chertow, GM
通讯作者：
Chertow, GM
影响因子：
37.8
作者：
Cooper, WA;O'Brien, SM;Peterson, ED
通讯作者：
Peterson, ED
影响因子：
9
作者：
Bihorac, Azra;Yavas, Sinan;Segal, Mark S.
通讯作者：
Segal, Mark S.
DOI：
10.1097/01.asn.0000130340.93930.dd
发表时间：
2004-06-01
影响因子：
13.6
作者：
Lassnigg, A;Schmidlin, D;Hiesmayr, M
通讯作者：
Hiesmayr, M
DOI：
10.1186/cc12503
发表时间：
2013-02-06
期刊：
Critical care (London, England)
影响因子：
--
作者：
Kashani K;Al-Khafaji A;Ardiles T;Artigas A;Bagshaw SM;Bell M;Bihorac A;Birkhahn R;Cely CM;Chawla LS;Davison DL;Feldkamp T;Forni LG;Gong MN;Gunnerson KJ;Haase M;Hackett J;Honore PM;Hoste EA;Joannes-Boyau O;Joannidis M;Kim P;Koyner JL;Laskowitz DT;Lissauer ME;Marx G;McCullough PA;Mullaney S;Ostermann M;Rimmelé T;Shapiro NI;Shaw AD;Shi J;Sprague AM;Vincent JL;Vinsonneau C;Wagner L;Walker MG;Wilkerson RG;Zacharowski K;Kellum JA
通讯作者：
Kellum JA