Prognostic enrichment design in clinical trials for autosomal dominant polycystic kidney disease: the HALT-PKD clinical trial
Prognostic enrichment design in clinical trials for autosomal dominant polycystic kidney disease: the HALT-PKD clinical trial
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DOI：
10.1093/ndt/gfw294
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发表时间：
2017-11-01
影响因子：
6.1
通讯作者：
Torres, Vicente E.
中科院分区：
文献类型：
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作者：
Irazabal, Maria V.;Abebe, Kaleab Z.;Torres, Vicente E.
背景轻度常染色体显性多囊肾病（ADPKD）患者在随机临床试验（RCT）中提供信息的可能性较小。我们之前开发了ADPKD的影像学分类（典型弥漫性囊肿分布1A-E类和非典型囊肿分布2类），用于RCT中的预后富集设计。我们研究了使用这种分类是否会增加检测严格血压（BP）控制对HALT-PKD早期疾病参与者的有益治疗效果的能力（研究A）。早期疾病HALT-PKD研究的事后分析，这是一项研究严格与标准血压控制对ADPKD患者总肾体积（TKV）增加率和估计肾小球滤过率（eGFR）下降率（eGFR > 60 mL/min/1.73 m）的影响的RCT。551名患者被两名观察员（98.2%一致性）分为1A级（6.2%）、1B级（20.3%）、1C级（34.1%）、1D级（22.1%）、1 E级（11.8%）和2级（5.4%）。从1A级到1 E级，TKV增加和eGFR下降变得更陡。严格的BP控制与TKV增加较慢相关，对eGFR下降速率没有显著的总体影响（前4个月较快，之后略微较慢）。合并1A和2级（最低严重程度）、1B和1C级（中等严重程度）以及1D和1 E级（最高严重程度），在1D和E级中检测到对TKV增加和eGFR下降的更强有益作用，患者人数较少。在设计ADPKD的RCT时，应使用预后富集策略，如图像分类，以增加其功效并降低其成本。
Background. Patients with mild autosomal dominant polycystic kidney disease (ADPKD) are less likely to be informative in randomized clinical trials (RCTs). We previously developed an imaging classification of ADPKD (typical diffuse cyst distribution Class 1A-E and atypical cyst distribution Class 2) for prognostic enrichment design in RCTs. We investigated whether using this classification would have increased the power to detect a beneficial treatment effect of rigorous blood pressure (BP) control on HALT-PKD participants with early disease (Study A).Methods. Post hoc analysis of the early disease HALT-PKD study, an RCT that studied the effect of rigorous versus standard BP control on rates of total kidney volume (TKV) increase and estimated glomerular filtration rate (eGFR) decline in ADPKD patients with eGFR > 60 mL/min/1.73 m(2).Results. Five hundred and fifty-one patients were classified by two observers (98.2% agreement) into Class 1A (6.2%), 1B (20.3%), 1C (34.1%), 1D (22.1%), 1E (11.8%) and 2 (5.4%). The TKV increase and eGFR decline became steeper from Class 1A through 1E. Rigorous BP control had been shown to be associated with slower TKV increase, without a significant overall effect on the rate of eGFR decline (faster in the first 4 months and marginally slower thereafter). Merging Classes 1A and 2 (lowest severity), 1B and 1C (intermediate severity) and 1D and 1E (highest severity) detected stronger beneficial effects on TKV increase and eGFR decline in Class 1D and E with a smaller number of patients.Conclusions. Strategies for prognostic enrichment, such as image classification, should be used in the design of RCTs for ADPKD to increase their power and reduce their cost.