Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease (ALADIN): a randomised, placebo-controlled, multicentre trial
Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease (ALADIN): a randomised, placebo-controlled, multicentre trial
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DOI：
10.1016/s0140-6736(13)61407-5
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发表时间：
2013-11-02
期刊：
影响因子：
168.9
通讯作者：
Ruggenenti, Piero
中科院分区：
文献类型：
--
作者：
Caroli, Anna;Perico, Norberto;Ruggenenti, Piero
背景常染色体显性遗传性多囊肾病进展缓慢，终末期肾病，目前尚无有效的治疗方法。一项初步研究表明，生长抑素类似物奥曲肽长效释放（LAR）可以在这种情况下肾保护。我们的目的是评估3年的奥曲肽，LAR治疗对肾脏和囊肿的生长和肾功能下降的参与者，这种disorder.Methods我们做了一个学术，多中心，随机，单盲，安慰剂对照，平行组试验在意大利的五家医院。成人（>18岁）肾小球滤过率（GFR）≥ 40 mL/min/1.73 m2的患者随机分配（通过电话与计算机列表进行中心分配，1：1比例，按中心分层，区组大小为4和8），接受奥曲肽-LAR（n=40）或0.9%氯化钠溶液（n=39）2次20 mg肌内注射，每28天1次，治疗3年。研究医生和护士知道分配的组;参与者和结局评估者对分配不知情。主要终点是1年和3年随访时通过MRI测量的肾脏总体积（TKV）的变化。本研究注册于ClinicalTrials.gov，NCT 00309283。结果招募时间为2006年4月27日至2008年5月12日。奥曲肽-LAR组38例患者和安慰剂组37例患者在1年随访时进行了可评价的MRI扫描，在该时间点，奥曲肽-LAR组的平均TKV增加（46.2 mL，SE 18.2）显著低于安慰剂组（143.7 mL，26.0; p=0.032）。在3年随访时，每组中有35例患者进行了可评价的MRI扫描，在该时间点，奥曲肽-LAR组的平均TKV增加（220.1 mL，49.1）在数值上小于安慰剂组（454.3 mL，80.8），但差异不显著（p=0.25）。奥曲肽-LAR组37例（92.5%）受试者和安慰剂组32例（82.1%）受试者至少发生1起不良事件（p=0.16）。发生严重不良事件的受试者在两个治疗组中的分布相似。然而，四例胆石症或急性胆囊炎发生在奥曲肽-LAR组，可能是treatment-related.Interpretation这些研究结果提供了背景的大型随机对照试验，以测试的保护作用，生长抑素类似物对肾功能丧失和进展到终末期肾病。
Background Autosomal dominant polycystic kidney disease slowly progresses to end-stage renal disease and has no effective therapy. A pilot study suggested that the somatostatin analogue octreotide longacting release (LAR) could be nephroprotective in this context. We aimed to assess the effect of 3 years of octreotide-LAR treatment on kidney and cyst growth and renal function decline in participants with this disorder.Methods We did an academic, multicentre, randomised, single-blind, placebo-controlled, parallel-group trial in five hospitals in Italy. Adult (>18 years) patients with estimated glomerular filtration rate (GFR) of 40 mL/min per 1.73 m(2) or higher were randomly assigned (central allocation by phone with a computerised list, 1:1 ratio, stratified by centre, block size four and eight) to 3 year treatment with two 20 mg intramuscular injections of octreotide-LAR (n=40) or 0.9% sodium chloride solution (n=39) every 28 days. Study physicians and nurses were aware of the allocated group; participants and outcome assessors were masked to allocation. The primary endpoint was change in total kidney volume (TKV), measured by MRI, at 1 year and 3 year follow-up. Analyses were by modified intention to treat. This study is registered with ClinicalTrials.gov, NCT00309283.Findings Recruitment was between April 27, 2006, and May 12, 2008. 38 patients in the octreotide-LAR group and 37 patients in the placebo group had evaluable MRI scans at 1 year follow-up, at this timepoint, mean TKV increased significantly less in the octreotide-LAR group (46.2 mL, SE 18.2) compared with the placebo group (143.7 mL, 26.0; p=0.032). 35 patients in each group had evaluable MRI scans at 3 year follow-up, at this timepoint, mean TKV increase in the octreotide-LAR group (220.1 mL, 49.1) was numerically smaller than in the placebo group (454.3 mL, 80.8), but the difference was not significant (p=0.25). 37 (92.5%) participants in the octreotide-LAR group and 32 (82.1%) in the placebo group had at least one adverse event (p=0.16). Participants with serious adverse events were similarly distributed in the two treatment groups. However, four cases of cholelithiasis or acute cholecystitis occurred in the octreotide-LAR group and were probably treatment-related.Interpretation These findings provide the background for large randomised controlled trials to test the protective effect of somatostatin analogues against renal function loss and progression to end-stage kidney disease.