Abstract
Background and Aims
Hyperphosphatemia in chronic kidney disease (CKD) patients is associated with adverse outcomes, including vascular calcification, increasing risks of disease progression and even death. Sevelamer carbonate have been approved in Europe for phosphate lowering treatment in pre-dialysis CKD patient, its efficacy and safety in Chinese CKD hyperphosphatemia patients are not previously reported.
Method
This was a phase III, multi-center, randomized, double blind, placebo-controlled, balanced (1:1, sevelamer: placebo) parallel-group study to evaluate the efficacy and safety of sevelamer carbonate versus placebo over 8 weeks’ duration in hyperphosphatemic CKD patients not on dialysis in China (Registration number NCT03001011). The primary objective of this study is to demonstrate efficacy of sevelamer carbonate tablets in the reduction of serum phosphorus in hyperphosphatemia in patients with chronic kidney disease (CKD) not on dialysis.
Results
In all, 202 patients were randomized (sevelamer, n=101; placebo, n=101); mean age was 50.7 years, 53.5% were male and the mean time of CKD diagnosis was 3.4 years with mean eGFR 7.5 ml/min/1.73 m2. The baseline phosphorous were 2.13±0.35 mmol/L and 2.12±0.37 mmol/L in sevelamer and placebo group, respectively. The mean serum phosphorous decreased significantly in patients treated with sevelamer carbonate (-0.22±0.47 mmol/L) compared with placebo (0.05±0.44 mmol/L) (mean difference between sevelamer carbonate and placebo was -0.26 mmol/L, P<0.0001). When compared with placebo, sevelamer carbonate significantly reduced serum total cholesterol (-0.90±0.85 vs. -0.06±0.68 mmol/L, P<0.0001), low-density lipoprotein cholesterol (-0.94±0.72 vs. -0.04±0.58 mmol/L, P<0.0001) and calcium-phosphorous product (-0.48±0.97 vs. 0.05±0.81 mmol2/L2) from baseline to week 8. Serum iPTH was not significantly changed in sevelamer carbonate group compared with placebo group (-9.60±136.00 vs. 7.61±141.92 ng/L, P=0.83). Sevelamer carbonate was well tolerated with 83.27% compliance compared with 82.19% compliance in placebo arm. Average dose of sevelamer carbonate was 7.51 g/d at the end of study and 4.52 g/d across the study. Adverse events experienced by patients in sevelamer carbonate and placebo group were similar.
Conclusion
This study demonstrated that sevelamer carbonate has produced a significant reduction of serum phosphorous, and is safe and tolerated in Chinese pre-dialysis CKD patients with hyperphosphatemia.
A randomized, crossover design study of sevelamer carbonate powder and sevelamer hydrochloride tablets in chronic kidney disease patients on haemodialysis