Higher strength lanthanum carbonate provides serum phosphorus control with a low tablet burden and is preferred by patients and physicians: a multicenter study

Abstract

Background and objectives: Management of hyperphosphatemia, a predictor of mortality in chronic kidney disease, is challenging. Nonadherence to dietary phosphate binders, in part, contributes to uncontrolled serum phosphorus levels. This phase IIIb trial assessed the efficacy of increased dosages (3000 to 4500 mg/d) of reformulated lanthanum carbonate (500-, 750-, and 1000-mg tablets) in nonresponders to dosages of up to 3000 mg/d.

Design, setting, participants, & measurements: This 8-wk study with a 4-mo open-label extension enrolled 513 patients who were undergoing maintenance hemodialysis. Patients who achieved serum phosphorus control at week 4 with <or=3000 mg/d lanthanum carbonate entered cohort A; nonresponders were randomly assigned to receive 3000, 3750, or 4500 mg/d (cohort B). The primary outcome measure was the control rate for predialysis serum phosphorus levels at the end of week 8, among patients in cohort B.

Results: At the end of week 4, 54% of patients achieved serum phosphorus control at dosages <or=3000 mg/d administered as one tablet per meal. Among patients who entered cohort B, control rates of 25, 38, and 32% for patients who were randomly assigned to 3000, 3750, or 4500 mg/d lanthanum carbonate, respectively, were achieved, with no increase in adverse events. Patients and physicians reported significantly higher levels of satisfaction with reformulated lanthanum carbonate compared with previous phosphate binders, partly because of reduced tablet burden with higher dosage strengths. Physicians and patients also expressed a preference for lanthanum carbonate over previous medication.

Conclusions: Reformulated lanthanum carbonate is an effective phosphate binder that may reduce daily tablet burden.

Figure 1.

Schematic of study design. All patients in cohort B took the same number of pills (active + placebo) to maintain blinding.

Figure 2.

Patient disposition throughout the study. The most common reasons for study discontinuation were adverse events (AE; 12.1%), protocol violation (10.3%), and withdrawal of consent (9.6%). Kidney transplantation, loss to follow-up, and death each led to discontinuation for <2% of patients. Similar trends were observed across various parts of the study.

Figure 3.

Predialysis serum phosphorus levels at baseline and weeks 4, 8, and 24 for intention-to-treat (ITT) population and cohort A. Dotted lines indicate the upper (5.5 mg/dl; 1.78 mmol/L) and lower (3.5 mg/dl; 1.13 mmol/L) ends of the Kidney Disease Outcomes Quality Initiative (KDOQI)-recommended range for serum phosphorus in patients with stage 5 chronic kidney disease (CKD). P < 0.0001 for serum phosphorus levels at weeks 4, 8, and 24 compared with baseline for both populations. *Means ± SD of three separate measurements taken during that week.

Figure 4.

Preference for and satisfaction with lanthanum carbonate treatment. (A) Patient and physician medication preference (ITT population). P < 0.0001 for binomial test procedure with null hypothesis of proportion = 0.5 for lanthanum carbonate versus equal preference and previous medication combined. (B) Overall patient and physician satisfaction with lanthanum carbonate treatment (ITT population).

Figure 5.

AE reported in cohort B.