A three-year randomized, double-blind, placebo-controlled study of lanreotide in stage 2/3 autosomal dominant polycystic kidney disease.

We tested whether the analogue lanreotide slows glomerular filtration rate (GFR) decline over three years in adults with ADPKD stages 2/3.

我们测试了类似物兰瑞肽是否能在3年内减缓2/3期ADPKD成人患者的肾小球滤过率（GFR）下降。

Methods

In this randomized, double-blind, placebo-controlledtrial, we enrolled adults with ADPKD and measured GFR (mGFR) 30-89 ml/min/1.73 m2.

在这项随机、双盲、安慰剂对照试验中，我们招募了ADPKD成人患者，并测量了他们的GFR（mGFR）为30-89 ml/min/1.73 m2。

Patients were randomized to receive monthly injections of lanreotide 120 mg or 0.9% sodium chloride placebo for three years.

患者被随机分配每月接受120 mg的兰瑞肽注射或0.9%的氯化钠安慰剂，为期三年。

The primary endpoint was mGFR slope (iohexol clearance) assessed at baseline, weeks 72 and 144 and analyzed with a linear mixed-effects model (LMM).

主要终点是基线、第72周和第144周评估的mGFR斜率（iohexol清除率），并用线性混合效应模型（LMM）进行分析。

Secondary endpoints included annual estimated GFR decline (creatinine-based, assessed at 11 scheduled visits), kidney events, quality of life, and safety.

次要终点包括每年估算的GFR下降（基于肌酐，评估于11次预定访问）、肾脏事件、生活质量以及安全性。

Due to slow enrollment, recruitment stopped after 144 of 180 planned participants.

由于招募速度缓慢，招募工作在计划的180名参与者中仅完成了144名后就停止了。

All randomized participants were included in the analysis (intention-to-treat).

所有随机参与者都被纳入分析（意向治疗分析）。

Results

The primary endpoint was not met: the model-derived annualized between-arm difference in mGFR trajectory was -0.3 ml/min/1.73 m2 per year (95% confidence interval-3.4 to 2.8).

主要终点未达到：模型推导出的两组间mGFR轨迹的年化差异为-0.3 ml/min/1.73 m2每年（95%置信区间-3.4至2.8）。

The time × lanreotide coefficient from the pre-specified creatinine-eGFR LMM was significant +1.2 ml/min/1.73 m2 per year (0.27 to 2.15); however, this signal was not replicated by cystatin C-eGFR nor urinary creatinine clearance, consistent with a non-GFR effect on creatinine physiology.

预设的肌酐-eGFR线性混合模型中，时间×兰瑞肽系数显著为+1.2 ml/min/1.73 m2每年（0.27至2.15）；然而，这一信号并未被胱抑素C-eGFR或尿肌酐清除率所复制，这与肌酐生理学上的非肾小球滤过率（non-GFR）效应一致。

Rates of kidney events and quality-of-life scores were similar between arms.

两组间的肾脏事件发生率和生活质量评分相似。

Gastrointestinal adverse events were more frequent with lanreotide.

胃肠道不良事件在兰瑞肽组中更为频繁。

Hypoglycemia occurred in 11.1% of lanreotide-treated versus 1.4% of placebo-treated participants.

低血糖发生在11.1%的兰瑞肽治疗参与者中，而在安慰剂治疗参与者中为1.4%。

Conclusions

Lanreotide did not slow mGFR decline in adults with stage 2/3 ADPKD.

兰瑞肽未能减缓2/3期常染色体显性多囊肾病（ADPKD）成人的mGFR下降。

The creatinine-eGFR signal is exploratory, not supported by muscle-mass-independent markers, and should be interpreted in the context of a negative primary endpoint.

肌酐-eGFR信号是探索性的，未得到肌肉质量无关标记物的支持，并且应该在阴性主要终点的背景下进行解释。

An unexpected hypoglycemia signal warrants proactive monitoring when considering lanreotide in this population.

在考虑将兰瑞肽用于这一人群时，意外的低血糖信号需要积极监测。

trial_registration

Registered at ClinicalTrials.gov with study number NCT02127437.

已在ClinicalTrials.gov注册，研究编号为NCT02127437。