Abstract 14686: Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Once-Daily ZS-9 for Treatment of Hyperkalemia: Achievement and Maintenance of K+ in Subgroup Analysis of Patients with Significant Renal Impairment and Heart Failure
Introduction: Renin-angiotensin-aldosterone inhibitor (RAASi) therapies improve outcomes for heart failure (HF) patients (pts) when given at high doses, but optimal treatment is often limited because of its association with hyperkalemia, a mortality risk factor which frequently develops in difficult-to-treat pts, such as those with chronic kidney disease (CKD) and HF. There is an unmet need to address hyperkalemia in this underserved population. ZS-9 is a nonabsorbed cation exchanger specifically designed to entrap K+ in the gut. ZS-9 acutely restored and maintained K+ in hyperkalemic pts in a large Phase 3 study. A subgroup analysis was performed in pts with significant renal impairment (eGFR<60) and history of HF from this study.
Methods: Pts (N=753) with K+ 5.0-6.5 mEq/L were randomized (1:1:1:1:1) to ZS-9 (1.25, 2.5, 5 or 10g) or placebo (PBO) orally 3x/day for 48hr (acute phase). Following this phase, pts with K+ 3.5-5.0 mEq/L (n=542) were randomized 1:1 to the same ZS-9 acute phase dose or PBO 1x/day on Days 3-15 (extended phase). RAASi were maintained during the study. Unpaired t-tests were used to compare serum K+ in pts treated with ZS-9 vs PBO.
Results: Of 753 pts, 240 (32%) had baseline eGFR<60 and HF. Mean baseline K+ was 5.4 mEq/L. At 48hr, significantly greater decreases in K+ were seen 5g (n=48) and 10g (n=46) ZS-9 (-0.56, and -0.88 mEq/L, respectively) compared with PBO (n=57, p<0.0001 for both; Figure). In the extended phase, baseline K+ was similar between 10g ZS-9 (n=20, 4.4 mEq/L) and PBO groups (n=21, 4.4 mEq/L). Pts on ZS-9 10g maintained normokalemia during the extended phase (4.4 mEq/L at Day 15; p<0.05) whereas K+ increased with PBO (5.0 mEq/L at Day 15). Similar results were seen with 5g ZS-9 (p<0.05).
Conclusions: ZS-9 may fulfill an important clinical unmet need in hyperkalemic pts with HF and significant renal impairment through the restoration and maintenance of normokalemia, thus permitting optimal use of cardio- and renoprotective RAASi therapies.
Author Disclosures: B. Singh: Research Grant; Modest; ZS Pharma, Keryx, Concert, Amgen, La Jolla Pharma, Questcor, La Jolla Pharma. Honoraria; Modest; Amgen. Consultant/Advisory Board; Modest; ZS Pharma, Concert, Amgen, Questcor, Concert, Keryx. Employment; Significant; ZS Pharma, as of 8/1/2014. After clinical trial was finished.. Speakers Bureau; Significant; Questcor. H.S. Rasmussen: Employment; Significant; ZS Pharma, Inc.. Ownership Interest; Significant; ZS Pharma, Inc. P.T. Lavin: Employment; Significant; Boston Biostatistics Research Foundation, Lavin Consulting, LLC. Consultant/Advisory Board; Significant; ZS Pharma, Inc. A. Yang: Employment; Significant; Xelay Acumen, Inc.. Ownership Interest; Significant; ZS Pharma, Inc.. Consultant/Advisory Board; Significant; ZS Pharma, Inc. M.A. El-Shahawy: Research Grant; Modest; Amgen, GSK, Celgene, Abbvie. Research Grant; Significant; ZS Pharma, Inc.. Consultant/Advisory Board; Significant; ZS Pharma, Inc..
- © 2014 by American Heart Association, Inc.