Baseline characteristics and enrichment results from the SONAR trial


Por: Heerspink H.J.L., Andress D.L., Bakris G., Brennan J.J., Correa-Rotter R., Hou F.F., Kitzman D.W., Kohan D., Makino H., McMurray J., Perkovic V., Tobe S., Wigderson M., Yi T., Parving H.-H., de Zeeuw D.

Publicada: 1 ene 2018
Resumen:
Aim: The SONAR trial uses an enrichment design based on the individual response to the selective endothelin receptor antagonist atrasentan on efficacy (the degree of the individual response in the urinary albumin-to-creatinine ratio [UACR]) and safety/tolerability (signs of sodium retention and acute increases in serum creatinine) to assess the effects of this agent on major renal outcomes. The patient population and enrichment results are described here. Methods: Patients with type 2 diabetes with an estimated glomerular filtration rate (eGFR) within 25 to 75 mL/min/1.73 m2 and UACR between 300 and 5000 mg/g were enrolled. After a run-in period, eligible patients received 0.75 mg/d of atrasentan for 6 weeks. A total of 2648 responder patients in whom UACR decreased by =30% compared to baseline were enrolled, as were 1020 non-responders with a UACR decrease of <30%. Patients who experienced a weight gain of >3 kg and in whom brain natriuretic peptide exceeded =300 pg/mL, or who experienced an increase in serum creatinine >20% (0.5 mg/dL), were not randomized. Results: Baseline characteristics were similar for atrasentan responders and non-responders. Upon entry to the study, median UACR was 802 mg/g in responders and 920 mg/g in non-responders. After 6 weeks of treatment with atrasentan, the UACR change in responders was -48.8% (95% CI, -49.8% to -47.9%) and in non-responders was -1.2% (95% CI, -6.4% to 3.9%). Changes in other renal risk markers were similar between responders and non-responders except for a marginally greater reduction in systolic blood pressure and eGFR in responders. Conclusions: The enrichment period has successfully identified a population with a profound UACR reduction without clinical signs of sodium retention in whom a large atrasentan effect on clinically important renal outcomes is possible. The SONAR trial aims to establish whether atrasentan confers renal protection. © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Filiaciones:
Heerspink H.J.L.:
 Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

Andress D.L.:
 Pharma Development, AbbVie, North Chicago, IL, United States

Bakris G.:
 Department of Medicine, Section of Endocrinology, ASH Comprehensive Hypertension Center, University of Chicago Medicine and Biological Sciences, Chicago, IL, United States

Brennan J.J.:
 Pharma Development, AbbVie, North Chicago, IL, United States

Correa-Rotter R.:
 Department of Nephrology and Mineral Metabolism, National Medical Science and Nutrition Institute Salvador Zubirán, Mexico City, Mexico

Hou F.F.:
 Department of Internal Medicine, Division of Nephrology, Nanfang Hospital, Southern Medical University

Kitzman D.W.:
 Wake Forest School of Medicine, Winston-Salem, NC, United States

Kohan D.:
 Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, UT, United States

Makino H.:
 Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University, Okayama-Shi, Japan

McMurray J.:
 BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom

Perkovic V.:
 Faculty of Medicine, George Institute for Global Health, UNSW Sydney, Newtown, NSW, Australia

Tobe S.:
 Department of Medicine, Division of Nephrology, Sunnybrook Health Sciences Centre, University of Toronto and the Northern Ontario School of Medicine, Toronto, ON, Canada

Wigderson M.:
 Pharma Development, AbbVie, North Chicago, IL, United States

Yi T.:
 Pharma Development, AbbVie, North Chicago, IL, United States

Parving H.-H.:
 Department of Medical Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

 Faculty of Health Science, Aarhus University, Aarhus, Denmark

de Zeeuw D.:
 Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
ISSN: 14628902
Editorial
BLACKWELL PUBLISHING, 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND, Estados Unidos America
Tipo de documento: Article
Volumen: 20 Número: 8
Páginas: 1829-1835
WOS Id: 000438340500004
ID de PubMed: 29604160

MÉTRICAS