Abstract
ABSTRACT
Aims/Introduction
To demonstrate noninferiority of continued sodium zirconium cyclosilicate therapy versus a potassium‐restricted diet in achieving normokalemia at Visit 7 (Days 28–42) in individuals with type 2 diabetes and hyperkalemia, using a noninferiority margin of −10 percentage points (one‐sided α = 0.025).
Materials and Methods
This multicenter, open‐label, randomized trial assigned participants in the full analysis set to the sodium zirconium cyclosilicate (
n
= 37) or the diet group (
n
= 39) for the primary noninferiority analysis. Normokalemia was defined as serum potassium 3.5–
Results
In the full analysis set, normokalemia occurred in 28/36 (77.8%) and 26/38 (68.4%) patients in the sodium zirconium cyclosilicate and diet groups, respectively (risk difference +9.4 percentage points; 95% confidence interval, −11.1 to +29.8; one‐sided
P
= 0.032), failing to demonstrate noninferiority. In the supportive per‐protocol set, normokalemia occurred in 26/31 (83.9%) versus 17/24 (70.8%) patients, and the noninferiority criterion was met (
P
= 0.020); this analysis is exploratory. Mean serum potassium levels at Visit 7 were lower in the sodium zirconium cyclosilicate group (adjusted difference −0.23 mEq/L; 95% confidence interval, −0.42 to −0.03;
P
= 0.026). Dietary fiber intake decreased in the diet group. No changes in quality of life were observed between the two groups during the study period. The frequency of adverse events was low; however, one sudden death occurred in the sodium zirconium cyclosilicate group.
Conclusions
The trial did not meet its primary endpoint: noninferiority of sodium zirconium cyclosilicate to the potassium‐restricted diet was not demonstrated in the full analysis set.