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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• 作者：Anna Caroli ; Norberto Perico ; Annalisa Perna ; Luca Antiga ; Paolo Brambilla ; Antonio Pisani ; Bianca Visciano ; Massimo Imbriaco ; Piergiorgio Messa ; Roberta Cerutti ; Mauro Dugo ; Luca Cancian ; Erasmo Buongiorno ; Antonio De Pascalis ; Flavio Gaspari ; Fabiola Carrara ; Nadia Rubis ; Silvia Pr ; ini ; Andrea Remuzzi ; Giuseppe Remuzzi ; et al.
• 刊名：The Lancet
• 出版年：2-8 November, 2013
• 年：2013
• 卷：382
• 期：9903
• 页码：1485-1495
• 全文大小：658 K

文摘

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Summary

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路73 m² 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路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 , .

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路2 mL, SE 18路2) compared with the placebo group (143路7 mL, 26路0; p=0路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路1 mL, 49路1) was numerically smaller than in the placebo group (454路3 mL, 80路8), but the difference was not significant (p=0路25). 37 (92路5%) participants in the octreotide-LAR group and 32 (82路1%) in the placebo group had at least one adverse event (p=0路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.

Funding

Polycystic Kidney Disease Foundation.