Longitudinal Assessment of the Effect of Atrasentan on Thoracic Bioimpedance in Diabetic Nephropathy

A Randomized, Double-Blind, Placebo-Controlled Trial

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalDrugs in R and D
DOIs
StateAccepted/In press - Aug 22 2017

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Diabetic Nephropathies
Thorax
Placebos
Type 2 Diabetes Mellitus
Hemoglobins
Serum
Hemodilution
Vital Signs
Brain Natriuretic Peptide
Serology
Renin-Angiotensin System
atrasentan
Chronic Renal Insufficiency
Diuretics
Sample Size
Weight Gain
Edema
Therapeutics
Body Weight
Population

ASJC Scopus subject areas

  • Pharmacology

Cite this

Longitudinal Assessment of the Effect of Atrasentan on Thoracic Bioimpedance in Diabetic Nephropathy : A Randomized, Double-Blind, Placebo-Controlled Trial. / Webb, David J.; Coll, Blai; Heerspink, Hiddo J.L.; Andress, Dennis; Pritchett, Yili; Brennan, John J.; Houser, Mark; Correa-Rotter, Ricardo; Kohan, Donald; Makino, Hirofumi; Perkovic, Vlado; Remuzzi, Giuseppe; Tobe, Sheldon W.; Toto, Robert; Busch, Robert; Pergola, Pablo; Parving, Hans Henrik; de Zeeuw, Dick.

In: Drugs in R and D, 22.08.2017, p. 1-8.

Research output: Contribution to journalArticle

Webb, DJ, Coll, B, Heerspink, HJL, Andress, D, Pritchett, Y, Brennan, JJ, Houser, M, Correa-Rotter, R, Kohan, D, Makino, H, Perkovic, V, Remuzzi, G, Tobe, SW, Toto, R, Busch, R, Pergola, P, Parving, HH & de Zeeuw, D 2017, 'Longitudinal Assessment of the Effect of Atrasentan on Thoracic Bioimpedance in Diabetic Nephropathy: A Randomized, Double-Blind, Placebo-Controlled Trial', Drugs in R and D, pp. 1-8. https://doi.org/10.1007/s40268-017-0201-0
Webb, David J. ; Coll, Blai ; Heerspink, Hiddo J.L. ; Andress, Dennis ; Pritchett, Yili ; Brennan, John J. ; Houser, Mark ; Correa-Rotter, Ricardo ; Kohan, Donald ; Makino, Hirofumi ; Perkovic, Vlado ; Remuzzi, Giuseppe ; Tobe, Sheldon W. ; Toto, Robert ; Busch, Robert ; Pergola, Pablo ; Parving, Hans Henrik ; de Zeeuw, Dick. / Longitudinal Assessment of the Effect of Atrasentan on Thoracic Bioimpedance in Diabetic Nephropathy : A Randomized, Double-Blind, Placebo-Controlled Trial. In: Drugs in R and D. 2017 ; pp. 1-8.
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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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T2 - A Randomized, Double-Blind, Placebo-Controlled Trial

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AU - Coll, Blai

AU - Heerspink, Hiddo J.L.

AU - Andress, Dennis

AU - Pritchett, Yili

AU - Brennan, John J.

AU - Houser, Mark

AU - Correa-Rotter, Ricardo

AU - Kohan, Donald

AU - Makino, Hirofumi

AU - Perkovic, Vlado

AU - Remuzzi, Giuseppe

AU - Tobe, Sheldon W.

AU - Toto, Robert

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AU - Pergola, Pablo

AU - Parving, Hans Henrik

AU - de Zeeuw, Dick

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