Evaluation of calcium acetate/magnesium carbonate as a phosphate binder compared with sevelamer hydrochloride in haemodialysis patients: a controlled randomized study (CALMAG study) assessing efficacy and tolerability

Abstract

Background: Phosphate binders are required to control serum phosphorus in dialysis patients. A phosphate binder combining calcium and magnesium offers an interesting therapeutic option.

Methods: This controlled randomized, investigator-masked, multicentre trial investigated the effect of calcium acetate/magnesium carbonate (CaMg) on serum phosphorus levels compared with sevelamer hydrochloride (HCl). The study aim was to show non-inferiority of CaMg in lowering serum phosphorus levels into Kidney Disease Outcome Quality Initiative (K/DOQI) target level range after 24 weeks. Three hundred and twenty-six patients from five European countries were included. After a phosphate binder washout period, 255 patients were randomized in a 1:1 fashion. Two hundred and four patients completed the study per protocol (CaMg, N = 105; dropouts N = 18; sevelamer-HCl, N = 99; dropouts N = 34). Patient baseline characteristics were similar in both groups.

Results: Serum phosphorus levels had decreased significantly with both drugs at week 25, and the study hypothesis of CaMg not being inferior to sevelamer-HCl was confirmed. The area under the curve for serum phosphorus (P = 0.0042) and the number of visits above K/DOQI (≤1.78 mmol/L, P = 0.0198) and Kidney disease: Improving global outcomes (KDIGO) targets (≤1.45 mmol/L, P = 0.0067) were significantly lower with CaMg. Ionized serum calcium did not differ between groups; total serum calcium increased in the CaMg group (treatment difference 0.0477 mmol/L; P = 0.0032) but was not associated with a higher risk of hypercalcaemia. An asymptomatic increase in serum magnesium occurred in CaMg-treated patients (treatment difference 0.2597 mmol/L, P < 0.0001). There was no difference in the number of patients with adverse events.

Conclusion: CaMg was non-inferior to the comparator at controlling serum phosphorus levels at Week 25. There was no change in ionized calcium; there was minimal increase in total serum calcium and a small increase in serum magnesium. It had a good tolerability profile and thus may represent an effective treatment of hyperphosphataemia.

Fig. 1

(A) Study design and procedure. (B) CONSORT diagram demonstrating patient flow including analysis sets.

Fig. 2

(A) Study medication intake per day and group over time in the CaMg group (n = 101) and the Sevelamer-HCl group (n = 90) (PPS); P = 0.0420 (ANOVA). (B) Time course of serum phosphorus over 24 weeks for the CaMg group (n = 105); and the sevelamer-HCl group (n = 99) (PPS).

Fig. 3

(A) Time course of ionized serum calcium of the CaMg group (n = 120) and of the sevelamer-HCl group (n = 119) (FAS); P = 0.9173 (ANCOVA). (B) Time course of total serum calcium of the CaMg group (n = 122) and of the sevelamer-HCl group (n = 122) (FAS); P = 0.0032 (ANCOVA).

Fig. 4

Time course of serum magnesium of the CaMg group (n = 122) and of the sevelamer-HCl group (n = 122) (FAS); P <0.0001 (ANCOVA).

Fig. 5

Time course of iPTH of the CaMg group (n = 118) and of the sevelamer-HCl group (n = 112) (FAS), P = 0.0085 (ANCOVA); within-group changes CaMg: *Week 9 vs baseline: P < 0.0001, **Week 25 vs Week 9: P = 0.0768; within-group changes sevelamer-HCL: * Week 9 vs baseline: P = 0.0090, ** Week 25 vs Week 9: P = 0.0242.