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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.

de Francisco AL, Leidig M, Covic AC, Ketteler M, Benedyk-Lorens E, Mircescu GM, Scholz C, Ponce P, Passlick-Deetjen J - Nephrol. Dial. Transplant. (2010)

Bottom Line: 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.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.It had a good tolerability profile and thus may represent an effective treatment of hyperphosphataemia.

View Article: PubMed Central - PubMed

Affiliation: Hospital Marques de Valdecilla, Universidad de Cantabria, Santander, Spain. angelmartindefrancisco@gmail.com

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.

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Related in: MedlinePlus

(A) Study design and procedure. (B) CONSORT diagram demonstrating patient flow including analysis sets.
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fig1: (A) Study design and procedure. (B) CONSORT diagram demonstrating patient flow including analysis sets.

Mentions: This prospective, controlled, randomized, multicentre, investigator-masked, parallel-group study compared tolerability and efficacy of two different oral phosphate binder treatments (CaMg and sevelamer-HCl) for 24 weeks in HD or online HDF patients. The primary endpoint of this trial was the exploration of the efficacy of CaMg compared with sevelamer-HCl as an active control. The primary target variable was serum phosphorus at Week 25. After a washout/run-in phase of 2 to 3 weeks, during which all phosphate binders had to be discontinued and all patients were switched to the study dialysis fluid composition (dialysate calcium of 1.5 or 1.25 mmol/L, dependent on prior prescription, and dialysate magnesium of 0.5 mmol/L) for at least 2 weeks, patients were randomized in a 1:1 ratio (Figure 1A). Randomization was central via Fax and stratified according to the dialysis mode (HD vs online HDF). The dialysate calcium composition was constant throughout the study at either 1.25 or 1.5 mmol/L. Only those patients being treated with a dialysate of 1.25 mmol/L during the study could be switched to a dialysate of 1.5 mmol/L in the event of hypocalcaemia.


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.

de Francisco AL, Leidig M, Covic AC, Ketteler M, Benedyk-Lorens E, Mircescu GM, Scholz C, Ponce P, Passlick-Deetjen J - Nephrol. Dial. Transplant. (2010)

(A) Study design and procedure. (B) CONSORT diagram demonstrating patient flow including analysis sets.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2957591&req=5

fig1: (A) Study design and procedure. (B) CONSORT diagram demonstrating patient flow including analysis sets.
Mentions: This prospective, controlled, randomized, multicentre, investigator-masked, parallel-group study compared tolerability and efficacy of two different oral phosphate binder treatments (CaMg and sevelamer-HCl) for 24 weeks in HD or online HDF patients. The primary endpoint of this trial was the exploration of the efficacy of CaMg compared with sevelamer-HCl as an active control. The primary target variable was serum phosphorus at Week 25. After a washout/run-in phase of 2 to 3 weeks, during which all phosphate binders had to be discontinued and all patients were switched to the study dialysis fluid composition (dialysate calcium of 1.5 or 1.25 mmol/L, dependent on prior prescription, and dialysate magnesium of 0.5 mmol/L) for at least 2 weeks, patients were randomized in a 1:1 ratio (Figure 1A). Randomization was central via Fax and stratified according to the dialysis mode (HD vs online HDF). The dialysate calcium composition was constant throughout the study at either 1.25 or 1.5 mmol/L. Only those patients being treated with a dialysate of 1.25 mmol/L during the study could be switched to a dialysate of 1.5 mmol/L in the event of hypocalcaemia.

Bottom Line: 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.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.It had a good tolerability profile and thus may represent an effective treatment of hyperphosphataemia.

View Article: PubMed Central - PubMed

Affiliation: Hospital Marques de Valdecilla, Universidad de Cantabria, Santander, Spain. angelmartindefrancisco@gmail.com

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.

Show MeSH
Related in: MedlinePlus