HARMONIZE Asia: A Phase III Randomized Study to Investigate the Efficacy and Safety of Sodium Zirconium Cyclosilicate in Patients with Hyperkalemia in China.
Clin Ther
; 46(9): 702-710, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-39112102
ABSTRACT
PURPOSE:
Sodium zirconium cyclosilicate (SZC) is an oral potassium (K+)-lowering therapy for adults with hyperkalemia. HARMONIZE Asia (ClinicalTrials.gov identifier NCT03528681) evaluated the efficacy and safety of SZC in Chinese patients with hyperkalemia.METHODS:
This Phase III, randomized, double-blind, placebo-controlled study recruited patients with serum K+ (sK+) ≥5.1 mmol/L at 35 sites in China. Patients received SZC 10 g three times daily (TID) for 24 or 48 hours during an open-label initial phase (OLP). Those patients achieving normokalemia (sK+ 3.5-5.0 mmol/L inclusive) entered a 28-day randomized (221) treatment phase (RTP) and received SZC 5 g, SZC 10 g, or placebo once daily. The primary endpoint was mean sK+ during RTP Days 8 to 29. Secondary endpoints included mean change in sK+ during the OLP, the proportion of patients who achieved normokalemia at the end of the OLP, the proportion that maintained normokalemia during the RTP, and time to recurrence of hyperkalemia.FINDINGS:
In total, 270 patients received SZC 10 g TID during the OLP; 256 (94.8%) completed the OLP. During the OLP, mean sK+ decreased by 1.1 mmol/L from baseline (5.9 mmol/L; P < 0.001) and 87.4% of patients achieved normokalemia. During the RTP, SZC 5 g and 10 g reduced mean sK+ versus placebo in a dose-dependent manner (each P < 0.001); least-squares means (95% confidence interval [CI]) sK+ were 4.9 mmol/L (4.7, 5.0), 4.4 mmol/L (4.3, 4.6), and 5.2 mmol/L (5.1, 5.4) for SZC 5 g, 10 g, and placebo, respectively. At RTP end, the proportions of patients who maintained normokalemia were 58.8% (SZC 5 g; odds ratio vs placebo, 2.5 [95% CI 1.1, 6.1; P = 0.035]), 76.5% (SZC 10 g; odds ratio vs placebo, 6.3 [95% CI 2.6, 15.3; P < 0.001]), and 36.8% for placebo. Risk of recurrent hyperkalemia was reduced by 61.0% and 84.0% with SZC 5 g and SZC 10 g, respectively, versus placebo (each P < 0.001). During the RTP, the incidence of adverse events was numerically higher with SZC 5 g (50.0% of patients) and 10 g (44.0%) versus placebo (36.0%); driven primarily by peripheral edema and constipation. IMPLICATIONS Both SZC doses demonstrated clinically relevant and statistically significant, dose-dependent efficacy in managing sK+ levels in Chinese patients with hyperkalemia, compared with placebo. SZC tolerability was broadly aligned with the known safety profile of SZC.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Silicatos
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Hiperpotasemia
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Asia
Idioma:
En
Revista:
Clin Ther
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos