Improvements in haemolysis and indicators of erythrocyte survival do not correlate with acute vaso-occlusive crises in patients with sickle cell disease: a phase III randomized, placebo-controlled, double-blind study of the gardos channel blocker senicapoc (ICA-17043)
Improvements in haemolysis and indicators of erythrocyte survival do not correlate with acute vaso-occlusive crises in patients with sickle cell disease: a phase III randomized, placebo-controlled, double-blind study of the gardos channel blocker senicapoc (ICA-17043)
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DOI：
10.1111/j.1365-2141.2010.08520.x
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发表时间：
2011-04-01
影响因子：
6.5
通讯作者：
Stocker, Jonathan W.
中科院分区：
文献类型：
--
作者：
Ataga, Kenneth I.;Reid, Marvin;Stocker, Jonathan W.
红细胞的水合作用部分由钙激活的钾离子外排通道调节。Senicapoc选择性地阻断钾通过Gardos通道流出，减少RBC脱水和溶血，并增加镰状细胞病（SCD）中的血红蛋白水平。这项随机、安慰剂对照试验旨在确定senicapoc在SCD患者中的安全性和临床疗效。145名患者随机接受senicapoc治疗，144名患者接受安慰剂治疗，持续52周。与先前的研究一致，与安慰剂组相比，senicapoc组患者的红细胞压积、血红蛋白显著增加，致密红细胞和网织红细胞数量减少。揭盲数据监测委员会由于缺乏疗效而提前终止了这项研究，因为它确定，尽管贫血和溶血有所改善，但与安慰剂组相比，在接受senicapoc治疗的患者中未观察到镰状细胞疼痛危象发生率的显著改善（分别为0中心点38 vs. 0中心点31）。senicapoc组和安慰剂组之间第一次、第二次和第三次危机的时间比较没有统计学意义。恶心和尿路感染在senicapoc组比安慰剂组更常见。两组的严重不良事件相似。
P>Red blood cell (RBC) hydration is regulated in part by the Ca2+-activated K+ efflux (Gardos) channel. Senicapoc selectively blocks potassium efflux through the Gardos channel, reducing RBC dehydration and haemolysis, and increasing haemoglobin levels in sickle cell disease (SCD). This randomized, placebo-controlled trial was designed to determine the safety and clinical efficacy of senicapoc in SCD patients. One hundred and forty-five patients were randomized to receive senicapoc and 144 patients to receive placebo for 52 weeks. Consistent with a previous study, patients in the senicapoc group had significantly increased haematocrit, haemoglobin, and decreased numbers of both dense erythrocytes and reticulocytes when compared to the placebo group. The unblinded Data Monitoring Committee terminated this study early due to a lack of efficacy when it determined that, despite improvements in anaemia and haemolysis, no significant improvement in the rate of sickle cell painful crises was observed in patients treated with senicapoc compared to those on placebo (0 center dot 38 vs. 0 center dot 31, respectively). Comparisons of the times to first, second and third crises between the senicapoc and placebo groups were not statistically significant. Nausea and urinary tract infections occurred more frequently in the senicapoc group than placebo. Serious adverse events were similar in the two groups.