Evaluation of the Efficacy and Safety of Sevelamer Carbonate for the Treatment of Hyperphosphatemia in Patients Receiving Hemodialysis. Results of a Prospective, Open-label, Multicenter Study
Sevelamer carbonate is a non-intestinal, calcium-free phosphate binder. Sevelamer carbonate controls hyperphosphatemia in dialysis and non-dialysis patients with renal insufficiency, without the concomitant risk of hypercalcemia. The phosphate-binding ability of this drug is clearly dose-dependent, and its lack of effectiveness in some patients may be associated with receiving it in an insufficient dose. Our study aimed to determine the average daily dose of sevelamer carbonate required to achieve a target serum phosphorus level of > 1.13 and < 1.78 mmol in real clinical practice in patients with chronic kidney disease (CKD) on hemodialysis. Material and methods. The study was a prospective, open-label, non-comparative, local, multicenter study conducted at 2 nephrology centers in the Russian Federation. The study consisted of 4 periods: a 2-week screening period, a 2-week washout period, a 12-week dose titration period, and a 12-week therapy period (active control period). The initial dose of sevelamer carbonate was determined in accordance with the initial level of phosphorus in the blood serum: 2.4 g per day for patients with a phosphorus level of1.78-2.42 mmol/l (5.5-7.5 mg/dl), and 4.8 g per day for patients with a phosphorus level > 2.42 mmol/l (> 7.5 mg/dl). The dose of sevelamer carbonate during the treatment period was titrated according to serum phosphorus levels. In patients, the levels of Ca and PTH were also monitored. Adverse events (AEs) were assessed from the time the informed consent was obtained until the end of the study. Results. 94patients were randomized to the study (52patients with baseline P 1.78-2.42 mmol/l and 42patients with P > 2.42 mmol/l). Of the 94 randomized patients, 86 (91,5%) completed the study. Serum phosphorus levels consistently decreased in all patients from a mean level of 2.43 ± 0.65 to 1.67 ± 0.47 mmol/l (p < 0.0001). In the group of patients with a maximum P level of up to 2.42 mmol/l, the average phosphorus level decreased from 1.92 ± 0.23 to 1.62 ± 0.31 mmol/l (p < 0.0001). In patients with high P levels (more than 2.42 mmol/l), the mean phosphorus level decreased from 3.05 ± 0.33 to 1.72 ± 0.44 mmol/l (p < 0.0001). The average daily dose of sevelamer carbonate in 2groups of patients was 5.63 ± 1.98 g, by the end of the study. The level of adjusted Ca decreased statistically significantly from 2.27 ± 0.12 to 2.04 ± 0.11 mmol/l (p < 0.001), the PTH level did not change. All study drug-related adverse events included gastrointestinal manifestations (nausea and constipation) and were expected based on previous studies. Conclusions. The use of sevelamer carbonate allowed to significantly reduce the level of phosphorus in all patients receiving hemodialysis, and in most patients the target levels of phosphorus in the blood were achieved. These results indicate that the use of sevelamer carbonate is effective and safe in patients with CKD and hyperphosphatemia.