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Abstract: TH-OR16

DIALIZE China: A Phase 3b Study to Reduce Pre-Dialysis Hyperkalemia With Sodium Zirconium Cyclosilicate in Chinese Subjects

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Zhao, June, AstraZeneca, Wilmington, Delaware, United States
  • Ni, Zhaohui, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • Lu, Renhua, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • Xu, Xudong, Central Hospital of Minhang District, Shanghai, China
  • Bian, Xueyan, Ningbo First Hospital, Ningbo, China
  • Zhihong, Zhou, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
  • Yang, Junwei, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
  • Luo, Qun, Ningbo Huamei Hospital, University of Chinese Academy of Sciences, Ningbo, China
  • Hua, Chen Meng, General Hospital of Ningxia Medical University, Yinchuan, China
  • Chen, Chaosheng, The First Affiliated Hospital of Wenzhou College, Wenzhou, China
  • Sun, Xiuli, Baotou City Central Hospital, Baotou, China
  • Yu, Lei, Inner Mongolia People’s Hospital, Hohhot, China
  • He, Qiang, Zhejiang Traditional Chinese Medicine Hospital, Hangzhou, China
  • Jiang, Hong, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang, China
  • Yuan, Wei jie, Shanghai General Hospital, Shanghai, China
  • Li, Yi, Dongguan People’s Hospital, Dongguan, China
  • Zhou, Rong, Shanghai Yangpu District Central Hospital, Shanghai, China
  • Jianqin, Wang, Lanzhou University Second Hospital, Lanzhou, China
  • Zhang, Xinzhou, Shenzhen People’s Hospital, Shenzhen, China
  • Zuo, Li, Peking University People’s Hospital, Beijing, China
  • Jin, Haijiao, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • Meng, Xiangwen, AstraZeneca, Shanghai, China
  • Chang, Zhiren, AstraZeneca, Shanghai, China

Group or Team Name

  • For the DIALIZE China Study Group.
Background

Sodium zirconium cyclosilicate (SZC) is an anti-hyperkalemia (HK) therapy (oral potassium binder) indicated in adults. DIALIZE China (NCT04217590) evaluated the safety and efficacy of SZC in individuals receiving hemodialysis (HD) in China.

Methods

DIALIZE China was a randomized, double-blind, placebo (PBO)-controlled, multicenter, phase 3b study of adults receiving HD 3-times weekly for kidney failure with pre-dialysis HK (serum potassium [sK+] >5.4 mmol/L after the long interdialytic interval [LIDI] and >5.0 mmol/L after 1 short interdialytic interval). Following a 1-week screening period, subjects were randomized 1:1 to SZC or PBO (5 g/day on non-dialysis days), titrated over 4 weeks up to 15 g/day as required to achieve normokalemia (NK; pre-dialysis sK+ 3.5–5.5 mmol/L), prior to a 4-week evaluation and 2-week follow-up. The primary outcome was the proportion of responders (pre-dialysis sK+ 4.0–5.0 mmol/L for ≥3 of 4 HD visits following the LIDI, without any rescue therapy during evaluation). Secondary outcomes included assessment of pre-dialysis sK+ values; safety outcomes included adverse events (AEs).

Results

Overall, 134 adults from China were randomized to SZC or PBO (each n=67); mean (SD) age was 54.7 (11.3) years, 49% were male and mean weight was 60 kg. There was a significantly higher proportion of responders in the SZC arm (37.3%) vs PBO arm (10.4%) (estimated odds ratio [OR]: 5.10, 95% CI: 1.90–15.12, P<0.001). A greater proportion of subjects achieved NK on ≥3 of 4 LIDI visits during evaluation with SZC (73%) than with PBO (30%). The probability of all pre-dialysis sK+ values being between ≥3.5 to ≤5.5 mmol/L was significantly higher with SZC vs PBO (estimated OR: 6.41, 95% CI: 2.71–15.12, P<0.001). AEs and serious AEs, respectively, occurred in 64% and 9% of subjects in the SZC arm, and 66% and 12% of subjects in the PBO arm, with no new safety concerns identified.

Conclusion

SZC is an effective and well-tolerated treatment for HK in Chinese individuals receiving HD.

Funding

  • Commercial Support – AstraZeneca