A Phase 3b, Randomized, Double-Blind, Placebo-Controlled Study of Sodium Zirconium Cyclosilicate for Reducing the Incidence of Predialysis Hyperkalemia

被引:128
作者
Fishbane, Steven [1 ]
Ford, Martin [2 ]
Fukagawa, Masafumi [3 ]
McCafferty, Kieran [4 ]
Rastogi, Anjay [5 ]
Spinowitz, Bruce [6 ]
Staroselskiy, Konstantin [7 ]
Vishnevskiy, Konstantin [8 ]
Lisovskaja, Vera [9 ]
Al-Shurbaji, Ayman [10 ]
Guzman, Nicolas [11 ]
Bhandari, Sunil [12 ]
机构
[1] Zucker Sch Med Hofstra Northwell, Dept Med, 100 Community Dr, Great Neck, NY 11021 USA
[2] Kings Coll Hosp NHS Trust, Dept Renal Med, London, England
[3] Tokai Univ, Sch Med, Dept Internal Med, Div Nephrol Endocrinol & Metab, Isehara, Kanagawa, Japan
[4] Barts Hlth NHS Trust, Dept Nephrol, London, England
[5] David Geffen Sch Med, Dept Med, Los Angeles, CA USA
[6] New York Presbyterian Queens, Dept Med, Queens, NY USA
[7] B Braun Avitum Russland Clin, Dept 2, St Petersburg, Russia
[8] First Pavlov State Med Univ St Petersburg, Propedeut Internal Dis Chair, St Petersburg, Russia
[9] AstraZeneca, Biometr & Informat, Gothenburg, Sweden
[10] AstraZeneca, Global Med Dev, Gothenburg, Sweden
[11] AstraZeneca, Global Med Dev, Gaithersburg, MD USA
[12] Hull Univ Teaching Hosp NHS Trust, Dept Renal & Transplant Med, Kingston Upon Hull, N Humberside, England
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2019年 / 30卷 / 09期
关键词
PORTABLE CLINICAL ANALYZER; SERUM POTASSIUM; HEMODIALYSIS-PATIENTS; SUDDEN-DEATH; DIALYSATE POTASSIUM; CARDIAC-ARREST; OUTCOMES; MORTALITY; SURVIVAL; DISEASE;
D O I
10.1681/ASN.2019050450
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background Patients with ESRD have minimal renal potassium excretion and, despite hemodialysis, often have persistent predialysis hyperkalemia. The DIALIZE study (NCT03303521) evaluated sodium zirconium cyclosilicate (SZC) in the management of hyperkalemia in hemodialysis patients. Methods In the DIALIZE study, a double-blind, placebo-controlled, phase 3b multicenter study, we randomized adults with ESRD who were managed by three-times weekly hemodialysis and had predialysis hyperkalemia to receive placebo or SZC 5 g once daily on non-dialysis days, and titrated towards maintaining normokalemia over 4 weeks, in 5 g increments to a maximum of 15 g. The primary efficacy outcome was proportion of patients during the 4-week stable-dose evaluation period who maintained predialysis serum potassium of 4.0-5.0 mmol/L during at least three of four hemodialysis treatments after the long interdialytic interval and did not require urgent rescue therapy to reduce serum potassium. Results In total, 196 patients (mean [standard deviation (SD)] age =58.1 [13.7] years old) were randomized to sodium zirconium cyclosilicate or placebo. Of 97 patients receiving sodium zirconium cyclosilicate, 41.2% met the primary end point and were deemed treatment responders compared with 1.0% of 99 patients receiving placebo (P<0.001). Rescue therapy to reduce serum potassium during the treatment period was required by 2.1% of patients taking sodium zirconium cyclosilicate versus 5.1% taking placebo. Serious adverse events occurred in 7% and 8% of patients in sodium zirconium cyclosilicate and placebo groups, respectively. The two groups displayed comparable interdialytic weight gain. There were few episodes of hypokalemia. Conclusions Sodium zirconium cyclosilicate is an effective and well-tolerated treatment for predialysis hyperkalemia in patients with ESRD undergoing adequate hemodialysis.
引用
收藏
页码:1723 / 1733
页数:11
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