Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease (ALADIN): a randomised, placebo-controlled, multicentre trial.

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 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.

FUNDING:

Polycystic Kidney Disease Foundation.

• Authors: 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 Prandini, Andrea Remuzzi, Giuseppe Remuzzi, Piero Ruggenenti, ALADIN study group
• Journal: Lancet (London, England) (Lancet) Vol. 382 Issue 9903 Pg. 1485-95 (Nov 02 2013) ISSN: 1474-547X [Electronic] England
• PMID: 23972263 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Gastrointestinal Agents
• Somatostatin
• Octreotide

Topics

• Adult
• Cholecystitis, Acute (chemically induced)
• Cholelithiasis (chemically induced)
• Disease Progression
• Female
• Follow-Up Studies
• Gastrointestinal Agents (adverse effects, therapeutic use)
• Humans
• Italy
• Kidney (drug effects, pathology)
• Kidney Failure, Chronic (prevention & control)
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Octreotide (adverse effects, therapeutic use)
• Organ Size (drug effects)
• Polycystic Kidney, Autosomal Dominant (drug therapy, pathology)
• Somatostatin (analogs & derivatives)
• Treatment Outcome