TY - JOUR
T1 - Pansomatostatin agonist pasireotide long-acting release for patients with autosomal dominant polycystic kidney or liver disease with severe liver involvement a randomized clinical trial
AU - Hogan, Marie C.
AU - Chamberlin, Julie A.
AU - Vaughan, Lisa E.
AU - Waits, Angela L.
AU - Banks, Carly
AU - Leistikow, Kathleen
AU - Oftsie, Troy
AU - Madsen, Chuck
AU - Edwards, Marie
AU - Glockner, James
AU - Kremers, Walter K.
AU - Harris, Peter C.
AU - Larusso, Nicholas F.
AU - Torres, Vicente E.
AU - Masyuk, Tatyana V.
N1 - Funding Information:
This publication was made possible by Mayo Translational Polycystic Kidney Disease Center grant DK090728; the Pirnie Family Foundation; National Center for Research Resources grant UL1 RR024150, a component of the National Institutes of Health; a National Institutes of Health Roadmap for Medical Research award (to M.C. Hogan); the Mayo Foundation for Medical Education and Research; resources in the Mayo Center for Translational Science Activities Center; and Novartis Pharma grant CSOM230XUS30T (to M.C. Hogan). This project was also supported by National Center for Advancing Translational Sciences grant UL1 TR002377. Acknowledgments We are indebted to Data Safety and Monitoring members (Dr. Gary L. Schwartz and Dr. Patrick S. Kamath), the patients who participated in the study, their families and physicians, and the Mayo Clinic Department of Internal Medicine Clinical Trials Unit that provided assistance with study implementation. The contents are solely the responsibility of the authors and do not necessarily represent the official view of the National Center for Research Resources or the National Institutes of Health.
Funding Information:
This publication was made possible by Mayo Translational PolycysticKidneyDiseaseCentergrantDK090728;thePirnieFamily Foundation; National Center for Research Resources grant UL1 RR024150, a component of the National Institutes of Health; a National Institutes of Health Roadmap for Medical Research award (to M.C. Hogan); the Mayo Foundation for Medical Education and Research; resources in the Mayo Center for Translational Science Activities Center; and Novartis Pharma grant CSOM230XUS30T (to M.C.Hogan).This projectwasalsosupportedbyNationalCenterfor Advancing Translational Sciences grant UL1 TR002377.
Publisher Copyright:
© 2020 by the American Society of Nephrology.
PY - 2020/9/7
Y1 - 2020/9/7
N2 - Background and objectives We assessed safety and efficacy of another somatostatin receptor analog, pasireotide long-acting release, in severe polycystic liver disease and autosomal dominant polycystic kidney disease. Pasireotide long-acting release, with its broader binding profile and higher affinity to known somatostatin receptors, has potential for greater efficacy. Design, setting, participants, & measurements Individuals with severe polycystic liver disease were assigned in a 2:1 ratio in a 1-year, double-blind, randomized trial to receive pasireotide long-acting release or placebo. Primary outcome was change in total liver volume; secondary outcomes were change in total kidney volume, eGFR, and quality of life. Results Of 48 subjects randomized, 41 completed total liver volume measurements (n=29 pasireotide long-acting release and n=12 placebo). From baseline, there were-99±189 ml/m absolute and-3%±7% change in annualized change in height-adjusted total liver volume (from 2582±1381 to 2479±1317 ml/m) in the pasireotide long-acting release group compared with 136±117 ml/m absolute and 6%±7% increase (from 2387±759 to 2533±770 ml/m) in placebo (P<0.001 for both). Total kidney volumes decreased by-12±34 ml/m and-1%±4% in pasireotide long-acting release compared with 21±21 ml/m and 4%±5% increase in the placebo group (P=0.05 for both). Changes in eGFR were similar between groups. Among the n=48 randomized, adverse events included hyperglycemia (26 of 33 [79%] in pasireotide long-acting release versus four of 15 [27%] in the placebo group; P<0.001), and among the 47 without diabetes at baseline, 19 of 32 (59%) in the pasireotide long-acting release group versus one of 15 (7%) in the placebo group developed diabetes (P=0.001). Conclusions Another somatostatin analog, pasireotide long-acting release, slowed progressive increase in both total liver volume/total kidney volume growth rates without affecting GFR decline. Participants experienced higher frequency of adverse events (hyperglycemia and diabetes). Clinical Trial registry name and registration number Pasireotide LAR in Severe Polycystic Liver Disease, NCT01670110.
AB - Background and objectives We assessed safety and efficacy of another somatostatin receptor analog, pasireotide long-acting release, in severe polycystic liver disease and autosomal dominant polycystic kidney disease. Pasireotide long-acting release, with its broader binding profile and higher affinity to known somatostatin receptors, has potential for greater efficacy. Design, setting, participants, & measurements Individuals with severe polycystic liver disease were assigned in a 2:1 ratio in a 1-year, double-blind, randomized trial to receive pasireotide long-acting release or placebo. Primary outcome was change in total liver volume; secondary outcomes were change in total kidney volume, eGFR, and quality of life. Results Of 48 subjects randomized, 41 completed total liver volume measurements (n=29 pasireotide long-acting release and n=12 placebo). From baseline, there were-99±189 ml/m absolute and-3%±7% change in annualized change in height-adjusted total liver volume (from 2582±1381 to 2479±1317 ml/m) in the pasireotide long-acting release group compared with 136±117 ml/m absolute and 6%±7% increase (from 2387±759 to 2533±770 ml/m) in placebo (P<0.001 for both). Total kidney volumes decreased by-12±34 ml/m and-1%±4% in pasireotide long-acting release compared with 21±21 ml/m and 4%±5% increase in the placebo group (P=0.05 for both). Changes in eGFR were similar between groups. Among the n=48 randomized, adverse events included hyperglycemia (26 of 33 [79%] in pasireotide long-acting release versus four of 15 [27%] in the placebo group; P<0.001), and among the 47 without diabetes at baseline, 19 of 32 (59%) in the pasireotide long-acting release group versus one of 15 (7%) in the placebo group developed diabetes (P=0.001). Conclusions Another somatostatin analog, pasireotide long-acting release, slowed progressive increase in both total liver volume/total kidney volume growth rates without affecting GFR decline. Participants experienced higher frequency of adverse events (hyperglycemia and diabetes). Clinical Trial registry name and registration number Pasireotide LAR in Severe Polycystic Liver Disease, NCT01670110.
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U2 - 10.2215/CJN.13661119
DO - 10.2215/CJN.13661119
M3 - Article
C2 - 32843370
AN - SCOPUS:85090323324
VL - 15
SP - 1267
EP - 1278
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
SN - 1555-9041
IS - 9
ER -