학술논문
Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease (ALADIN): a randomised, placebo-controlled, multicentre trial.
Document Type
Article
Author
Caroli, Anna; Perico, Norberto; Perna, Annalisa; Antiga, Luca; Brambilla, Paolo; Pisani, Antonio; Visciano, Bianca; Messa, Piergiorgio; Cerutti, Roberta; Dugo, Mauro; Cancian, Luca; Buongiomo, Erasmo; De Pascalis, Antonio; Gaspari, Flavio; Carrara, Fabiola; Rubis, Nadia; Prandini, Silvia; Remuzzi, Andrea; Remuzzi, Guiseppe; Ruggenenti, Piero
Source
Subject
*KIDNEY diseases
*OCTREOTIDE acetate
*POLYCYSTIC kidney disease
*SOMATOSTATIN
*CHRONIC kidney failure
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Language
ISSN
0140-6736
Abstract
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 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 • 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 évaluable 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 [ABSTRACT FROM AUTHOR]