학술논문
Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR):a double-blind, randomised, placebo-controlled trial
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Heerspink , H J L , Parving , H H , Andress , D L , Bakris , G , Correa-Rotter , R , Hou , F F , Kitzman , D W , Kohan , D , Makino , H , McMurray , J J V , Melnick , J Z , Miller , M G , Pergola , P E , Perkovic , V , Tobe , S , Yi , T , Wigderson , M , de Zeeuw , D , SONAR Committees and Investigators , Elbert , A , Vallejos , A , Alvarisqueta , A , Maffei , L , Juncos , L , de Arteaga , J , Greloni , G , Farias , E , Zucchini , A , Vogel , D , Cusumano , A , Santos , J , Fraenkel , M , Gallagher , M , Davis , T , Acharya , S , Cooke , D , Suranyi , M , Roger , S , Toussaint , N , Pollock , C , Chan , D , Stranks , S , MacIsaac , R , Endre , Z , Schmidt , A , Prager , R , Mayer , G , Warling , X , Jadoul , M , Egstrup , K , Oczachowska-Kulik , A E , Rossing , P , Ono , Y , Yalcin , M & Karim , S 2019 , ' Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR) : a double-blind, randomised, placebo-controlled trial ' , The Lancet , vol. 393 , no. 10184 , pp. 1937-1947 .
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Abstract
Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR