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Baseline characteristics and enrichment results from the SONAR trial.
- Source :
-
Diabetes, obesity & metabolism [Diabetes Obes Metab] 2018 Aug; Vol. 20 (8), pp. 1829-1835. Date of Electronic Publication: 2018 May 01. - Publication Year :
- 2018
-
Abstract
- 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.<br />Methods: Patients with type 2 diabetes with an estimated glomerular filtration rate (eGFR) within 25 to 75 mL/min/1.73 m <superscript>2</superscript> 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.<br />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.<br />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.<br /> (© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)
- Subjects :
- Aged
Angiotensin Receptor Antagonists therapeutic use
Angiotensin-Converting Enzyme Inhibitors therapeutic use
Antihypertensive Agents therapeutic use
Atrasentan adverse effects
Diabetic Angiopathies complications
Diabetic Nephropathies complications
Diabetic Nephropathies epidemiology
Diuretics therapeutic use
Double-Blind Method
Drug Resistance
Drug Therapy, Combination adverse effects
Endothelin A Receptor Antagonists adverse effects
Female
Glomerular Filtration Rate drug effects
Humans
Hypertension complications
Male
Middle Aged
Renal Insufficiency complications
Renal Insufficiency epidemiology
Renal Insufficiency prevention & control
Risk
Atrasentan therapeutic use
Diabetes Mellitus, Type 2 complications
Diabetic Angiopathies drug therapy
Diabetic Nephropathies prevention & control
Endothelin A Receptor Antagonists therapeutic use
Hypertension drug therapy
Precision Medicine
Subjects
Details
- Language :
- English
- ISSN :
- 1463-1326
- Volume :
- 20
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Diabetes, obesity & metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 29604160
- Full Text :
- https://doi.org/10.1111/dom.13315