Department of Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA.
Nephrol Dial Transplant. 2011 Dec;26(12):4095-103. doi: 10.1093/ndt/gfr363. Epub 2011 Jul 12.
Adult maintenance hemodialysis (MHD) patients experience high mortality and morbidity and poor quality of life (QoL). Markers of protein-energy wasting are associated with these poor outcomes. The OPPORTUNITY™ Trial examined whether recombinant human growth hormone (hGH) reduces mortality in hypoalbuminemic MHD patients. Secondary end points were effects on number of hospitalizations, cardiovascular events, lean body mass (LBM), serum proteins, exercise capacity, QoL and adverse events.
We performed a randomized, double-blind, placebo-controlled, multicenter multinational trial stratified for diabetic status. Clinically, stable adult MHD patients with serum albumin <4.0 g/dL were randomized to subcutaneous injections of hGH, 20 μg/kg/day, or placebo. Planned treatment duration was 24 months for 2500 patients. The trial was terminated early due to slow recruitment.
Seven hundred and twelve patients were randomized until trial termination; 695 patients received at least one dose of trial medication. Mean treatment duration was 20 weeks (no completers). There were no differences between groups in all-cause mortality, cardiovascular morbidity or mortality, serum albumin, LBM, physical exercise capacity or QoL. The hGH group, compared to placebo, displayed a reduction in body weight, total body fat, serum high-sensitivity C-reactive protein and possibly homocysteine and an increase in serum high-density lipoprotein-cholesterol and transferrin levels.
Although the OPPORTUNITY™ Trial was terminated early, treatment with hGH, compared to placebo, improved certain cardiovascular risk factors but did not reduce mortality, cardiovascular events or improve nutritional factors or QoL. The power for showing differences was substantially reduced due to the marked decrease in treatment duration and sample size.
成人维持性血液透析（MHD）患者死亡率和发病率高，生活质量（QoL）差。蛋白质能量消耗的标志物与这些不良结局相关。OPPORTUNITY™试验研究了重组人生长激素（hGH）是否降低低白蛋白血症 MHD 患者的死亡率。次要终点是对住院次数、心血管事件、瘦体质量（LBM）、血清蛋白、运动能力、QoL 和不良事件的影响。
我们进行了一项随机、双盲、安慰剂对照、多中心多国试验，按糖尿病状态分层。临床稳定的成人 MHD 患者血清白蛋白 <4.0 g/dL，随机接受皮下注射 hGH，20 μg/kg/天或安慰剂。计划治疗时间为 2500 例患者 24 个月。由于招募缓慢，试验提前终止。
712 例患者随机分组至试验终止；695 例患者至少接受了一次试验药物治疗。平均治疗时间为 20 周（无完成者）。两组之间全因死亡率、心血管发病率或死亡率、血清白蛋白、LBM、体力活动能力或 QoL 均无差异。与安慰剂组相比，hGH 组体重、总体脂、血清高敏 C 反应蛋白水平降低，可能的同型半胱氨酸水平降低，血清高密度脂蛋白胆固醇和转铁蛋白水平升高。
尽管 OPPORTUNITY™试验提前终止，但与安慰剂相比，hGH 治疗改善了某些心血管危险因素，但并未降低死亡率、心血管事件发生率，也未改善营养因素或 QoL。由于治疗持续时间和样本量明显减少，显示差异的能力大大降低。
