Forum report: Issues in clinical trials of empirical antifungal therapy in treating febrile neutropenic patients
Forum report: Issues in clinical trials of empirical antifungal therapy in treating febrile neutropenic patients
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DOI：
10.1086/367839
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发表时间：
2003-04-15
影响因子：
11.8
通讯作者：
Verweij, P
中科院分区：
文献类型：
--
作者：
Bennett, JE;Powers, J;Verweij, P
有推论证据表明，一些患者长期中性粒细胞减少和发热，抗菌药物无效，有足够的风险，深部真菌病，以保证经验性治疗，虽然抗真菌药物优于安慰剂尚未得到最终证明。两性霉素B脱氧胆酸盐、两性霉素B脂质体和伊曲康唑静脉注射后口服伊曲康唑溶液在美国获得许可用于该适应症。氟康唑和伏立康唑分别在低风险和高风险深部真菌感染患者的临床试验中获得了良好的结果。可能深刻影响经验性试验结果的设计特征是（1）纳入低风险患者，（2）研究未设盲，（3）通过改变抗菌抗生素来掩盖抗真菌作用，（4）在既往接受抗真菌预防或患有严重合并症的患者方面，未能平衡研究的两组，（5）将评价安全性的终点与评价有效性的终点合并;（6）选择不同的发热消退标准。
There is inferential evidence that some patients with prolonged neutropenia and fever not responding to antibacterial agents are at sufficient risk of deep mycoses to warrant empirical therapy, although superiority of an antifungal agent over placebo has not been conclusively demonstrated. Amphotericin B deoxycholate, liposomal amphotericin B, and intravenous itraconazole followed by oral itraconazole solution are licensed in the United States for this indication. Fluconazole and voriconazole have given favorable results in clinical trials of patients with low and high risk of deep mold infections, respectively. Design features that can profoundly influence outcome of empirical trials are (1) inclusion of low-risk patients, (2) failure to blind the study, (3) obscuration of antifungal effects by changing antibacterial antibiotics, (4) failure to balance both arms of the study in terms of patients with prior antifungal prophylaxis or with severe comorbidities, (5) the merging of end points evaluating safety with those of efficacy, and (6) choice of different criteria for resolution of fever.