Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG)
Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG)
复制标题
DOI：
10.1016/s0140-6736(11)60355-3
复制
发表时间：
2011-05-14
期刊：
影响因子：
168.9
通讯作者：
Thompson, Bruce W.
中科院分区：
文献类型：
--
作者：
Wang, Winfred C.;Ware, Russell E.;Thompson, Bruce W.
背景镰状细胞贫血与出生后第一年开始的急性并发症和器官功能障碍有关。羟基脲可显著减少镰状细胞贫血成人患者的疼痛和急性胸部综合征发作、住院和输血。我们评估了对器官功能障碍和临床并发症的羟基脲治疗的效果，并检查实验室检查结果和毒性effects. Methods这项随机试验进行了13个中心之间，2003年10月，2009年9月，在美国。符合条件的受试者患有血红蛋白SS（HbSS）或血红蛋白S β（0）地中海贫血，随机化时年龄为9 - 18个月，未根据临床严重程度选择。受试者接受液体羟基脲，每天20 mg/kg，或安慰剂2年。由医学协调中心按照预先确定的时间表进行随机分配。使用外观和味道相同的制剂用于羟基脲和安慰剂。患者、护理人员和协调中心工作人员对治疗分配情况不知情。主要研究终点为脾功能（Tc-99脾扫描定性摄取）和肾功能（通过Tc-99m-DTPA清除率测定的肾小球滤过率）。其他评估包括血细胞计数、胎仔血红蛋白浓度、化学特征、脾功能生物标志物、尿渗透压、神经发育、经颅多普勒超声检查、生长和致突变性。研究访视每2 - 4周进行一次。该试验在www.example.com注册，编号NCT 00006400。结果96名患者接受了羟基脲和97名安慰剂，其中羟基脲组83名患者和安慰剂组84名患者完成了研究。两组之间在主要终点方面没有观察到显着差异（在70名患者中，有19名患者在出院时脾功能下降，而安慰剂组中有28名患者在出院时脾功能下降，p = 0.21;在DTPA肾小球滤过率方面，羟基脲组与安慰剂组的平均增幅差异为2 ml/min/1.73 m2，p = 0.84）。羟基脲显著降低了疼痛（62例患者177起事件vs安慰剂组75例患者375起事件，p = 0.002）和指（趾）炎（14例患者24起事件vs安慰剂组42例患者123起事件，p
Background Sickle-cell anaemia is associated with substantial morbidity from acute complications and organ dysfunction beginning in the first year of life. Hydroxycarbamide substantially reduces episodes of pain and acute chest syndrome, admissions to hospital, and transfusions in adults with sickle-cell anaemia. We assessed the effect of hydroxycarbamide therapy on organ dysfunction and clinical complications, and examined laboratory findings and toxic effects.Methods This randomised trial was undertaken in 13 centres in the USA between October, 2003, and September, 2009. Eligible participants had haemoglobin SS (HbSS) or haemoglobin S beta(0)thalassaemia, were aged 9-18 months at randomisation, and were not selected for clinical severity. Participants received liquid hydroxycarbamide, 20 mg/kg per day, or placebo for 2 years. Randomisation assignments were generated by the medical coordinating centre by a pre-decided schedule. Identical appearing and tasting formulations were used for hydroxycarbamide and placebo. Patients, caregivers, and coordinating centre staff were masked to treatment allocation. Primary study endpoints were splenic function (qualitative uptake on Tc-99 spleen scan) and renal function (glomerular filtration rate by Tc-99m-DTPA clearance). Additional assessments included blood counts, fetal haemoglobin concentration, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Study visits occurred every 2-4 weeks. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00006400.Findings 96 patients received hydroxycarbamide and 97 placebo, of whom 83 patients in the hydroxycarbamide group and 84 in the placebo group completed the study. Significant differences were not seen between groups for the primary endpoints (19 of 70 patients with decreased spleen function at exit in the hydroxycarbamide group vs 28 of 74 patients in the placebo group, p=0.21; and a difference in the mean increase in DTPA glomerular filtration rate in the hydroxycarbamide group versus the placebo group of 2 ml/min per 1.73 m(2), p=0.84). Hydroxycarbamide significantly decreased pain (177 events in 62 patients vs 375 events in 75 patients in the placebo group, p=0.002) and dactylitis (24 events in 14 patients vs 123 events in 42 patients in the placebo group, p