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Published in: Drugs in R&D 3/2017

Open Access 01-09-2017 | Original Research Article

Longitudinal Assessment of the Effect of Atrasentan on Thoracic Bioimpedance in Diabetic Nephropathy: A Randomized, Double-Blind, Placebo-Controlled Trial

Authors: David J. Webb, Blai Coll, Hiddo J. L. Heerspink, Dennis Andress, Yili Pritchett, John J. Brennan, Mark Houser, Ricardo Correa-Rotter, Donald Kohan, Hirofumi Makino, Vlado Perkovic, Giuseppe Remuzzi, Sheldon W. Tobe, Robert Toto, Robert Busch, Pablo Pergola, Hans-Henrik Parving, Dick de Zeeuw

Published in: Drugs in R&D | Issue 3/2017

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Abstract

Background

Fluid retention is a common adverse event in patients who receive endothelin (ET) receptor antagonist therapy, including the highly selective ETA receptor antagonist, atrasentan.

Objective

We performed longitudinal assessments of thoracic bioimpedance in patients with type 2 diabetes mellitus and nephropathy to determine whether a decrease in bioimpedance accurately reflected fluid retention during treatment with atrasentan.

Study Design

We conducted a randomized, double-blind, placebo-controlled study in 48 patients with type 2 diabetes mellitus and nephropathy who were receiving stable doses of renin angiotensin system inhibitors and diuretics.

Methods

Patients were randomized 1:1:1 to placebo, atrasentan 0.5 mg, or atrasentan 1.25 mg once daily for 8 weeks. Thoracic bioimpedance, vital signs, clinical exams, and serologies were taken at weeks 1, 2, 4, 6, and 8, with the exception of serum hemoglobin, which was not taken at week 1, and serum brain natriuretic peptide, which was only taken at baseline, week 4, and week 8.

Results

Alterations in bioimpedance were more often present in those who received atrasentan than in those who received placebo, though overall differences were not statistically significant. Transient declines in thoracic bioimpedance during the first 2 weeks of atrasentan exposure occurred before or during peak increases in body weight and hemodilution (decreased serum hemoglobin).

Conclusions

We conclude that thoracic bioimpedance did not reflect changes in weight gain or edema with atrasentan treatment in this study. However, the sample size was small, and it may be of interest to explore the use of thoracic bioimpedance in a larger population to understand its potential clinical use in monitoring fluid retention in patients with chronic kidney disease who receive ET receptor antagonists.
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Metadata
Title
Longitudinal Assessment of the Effect of Atrasentan on Thoracic Bioimpedance in Diabetic Nephropathy: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors
David J. Webb
Blai Coll
Hiddo J. L. Heerspink
Dennis Andress
Yili Pritchett
John J. Brennan
Mark Houser
Ricardo Correa-Rotter
Donald Kohan
Hirofumi Makino
Vlado Perkovic
Giuseppe Remuzzi
Sheldon W. Tobe
Robert Toto
Robert Busch
Pablo Pergola
Hans-Henrik Parving
Dick de Zeeuw
Publication date
01-09-2017
Publisher
Springer International Publishing
Published in
Drugs in R&D / Issue 3/2017
Print ISSN: 1174-5886
Electronic ISSN: 1179-6901
DOI
https://doi.org/10.1007/s40268-017-0201-0

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