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Lanthanum carbonate reduces phosphorus burden in patients with CKD stages 3 and 4: a randomized trial.

ABSTRACT: Lanthanum carbonate (FOSRENOL, Shire Pharmaceuticals) is an effective noncalcium, nonresin phosphate binder for the control of hyperphosphatemia in chronic kidney disease (CKD) stage 5 patients undergoing dialysis.A Phase 2, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of lanthanum carbonate in CKD stage 3 and 4 patients. Of 281 patients screened, 121 were randomized (2:1) to lanthanum carbonate or placebo (80 versus 41). The modified intent-to-treat population included 90 patients (56 versus 34); 71 (43 versus 28) completed the study. After run-in, when any current phosphate binders were discontinued and dietary counseling reinforced, patients with serum phosphorus >4.6 mg/dl received lanthanum carbonate (titrated up to 3000 mg/d) or matching placebo for 8 wk.At the end of treatment, 25 (44.6%) versus nine (26.5%) patients had serum phosphorus < or =4.6 mg/dl (difference 18.1%, P = 0.12) in the lanthanum carbonate and placebo groups, respectively. Statistically significant differences were observed between groups in change from baseline to end of treatment for serum phosphorus (P = 0.02), intact parathyroid hormone (P = 0.02), and urinary phosphorus excretion (P = 0.04). The safety profile and tolerability of lanthanum carbonate were similar to that of placebo.Because <1% of phosphorus is in the extracellular fluid, serum measurements may not accurately reflect total body burden in patients with CKD stages 3 and 4. However, lanthanum carbonate is an effective phosphate binder in this patient population, with a safety profile and tolerability similar to that of placebo.

SUBMITTER: Sprague SM

PROVIDER: S-EPMC2615694 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Lanthanum carbonate reduces phosphorus burden in patients with CKD stages 3 and 4: a randomized trial.

Sprague Stuart M SM Abboud Hanna H Qiu Ping P Dauphin Matthew M Zhang Pinggao P Finn William W

Clinical journal of the American Society of Nephrology : CJASN 20081203 1

<h4>Background and objectives</h4>Lanthanum carbonate (FOSRENOL, Shire Pharmaceuticals) is an effective noncalcium, nonresin phosphate binder for the control of hyperphosphatemia in chronic kidney disease (CKD) stage 5 patients undergoing dialysis.<h4>Design, setting, participants and measurements</h4>A Phase 2, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of lanthanum carbonate in CKD stage 3 and 4 patients. Of 281 patients screened, 121 were randomized ...[more]

PMID: 19056618

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Project description:ImportanceAmong patients with hyperphosphatemia undergoing dialysis, it is unclear whether non-calcium-based phosphate binders are more effective than calcium-based binders for reducing cardiovascular events.ObjectiveTo determine whether lanthanum carbonate reduces cardiovascular events compared with calcium carbonate in patients with hyperphosphatemia at risk of vascular calcification undergoing hemodialysis.Design, setting, and participantsOpen-label, randomized, parallel-group clinical trial with blinded end point adjudication performed in 2374 patients with chronic kidney disease from 273 hemodialysis facilities in Japan. Eligible patients had hyperphosphatemia and 1 or more risk factors for vascular calcification (ie, ≥65 years, postmenopausal, diabetes). Enrollment occurred from November 2011 to July 2014; follow-up ended June 2018.InterventionsPatients were randomized to receive either lanthanum carbonate (n = 1154) or calcium carbonate (n = 1155) and titrated to achieve serum phosphate levels of between 3.5 mg/dL and 6.0 mg/dL.Main outcomes and measuresThe primary outcome was a composite cardiovascular event (cardiovascular death, nonfatal myocardial infarction or stroke, unstable angina, transient ischemic attack, or hospitalization for heart failure or ventricular arrhythmia). Secondary outcomes included overall survival, secondary hyperparathyroidism-free survival, hip fracture-free survival, and adverse events.ResultsAmong 2309 randomized patients (median age, 69 years; 40.5% women), 1851 (80.2%) completed the trial. After a median follow-up of 3.16 years, cardiovascular events occurred in 147 of 1063 patients in the lanthanum calcium group and 134 of 1072 patients in the calcium carbonate group (incidence rate, 4.80 vs 4.30 per 100 person-years; difference 0.50 per 100 person-years [95% CI, -0.57 to 1.56]; hazard ratio [HR], 1.11 [95%, CI, 0.88 to 1.41], P = .37). There were no significant differences in all-cause death (difference, 0.43 per 100 person-years [95% CI, -0.63 to 1.49]; HR, 1.10 [95% CI, 0.88 to 1.37]; P = .42) or hip fracture (difference, 0.10 per 100 person-years [95% CI, -0.26 to 0.47]; HR, 1.21 [95% CI, 0.62 to 2.35]; P = .58). The lanthanum carbonate group had an increased risk of cardiovascular death (difference, 0.61 per 100 person-years [95% CI, 0.02 to 1.21]; HR, 1.51 [95% CI, 1.01 to 2.27]; P = .045) and secondary hyperparathyroidism (difference, 1.34 [95% CI, 0.49 to 2.19]; HR, 1.62 [95% CI, 1.19 to 2.20]; P = .002). Adverse events occurred in 282 (25.7%) in the lanthanum carbonate group and 259 (23.4%) in the calcium carbonate groups.Conclusions and relevanceAmong patients undergoing hemodialysis with hyperphosphatemia and at least 1 vascular calcification risk factor, treatment of hyperphosphatemia with lanthanum carbonate compared with calcium carbonate did not result in a significant difference in composite cardiovascular events. However, the event rate was low, and the findings may not apply to patients at higher risk.Trial registrationClinicalTrials.gov Identifier: NCT01578200; UMIN Clinical Trial Registry Identifier: UMIN000006815.

Project description:Background:Inadequate protein intake and hypoalbuminemia, indicators of protein-energy wasting, are among the strongest mortality predictors in hemodialysis patients. Hemodialysis patients are frequently counseled on dietary phosphorus restriction, which may inadvertently lead to decreased protein intake. We hypothesized that, in hypoalbuminemic hemodialysis patients, provision of high-protein meals during hemodialysis combined with a potent phosphorus binder increases serum albumin without raising phosphorus levels. Methods:We conducted a randomized controlled trial in 110 adults undergoing thrice-weekly hemodialysis with serum albumin <4.0 g/dL recruited between July 2010 and October 2011 from eight Southern California dialysis units. Patients were randomly assigned to receive high-protein (50-55 g) meals during dialysis, providing 400-500 mg phosphorus, combined with lanthanum carbonate versus low-protein (<1 g) meals during dialysis, providing <20 mg phosphorus. Prescribed nonlanthanum phosphorus binders were continued over an 8-week period. The primary composite outcome was a rise in serum albumin of ?0.2 g/dL while maintaining phosphorus between 3.5-<5.5 mg/dL. Secondary outcomes included achievement of the primary outcome's individual endpoints and changes in mineral and bone disease and inflammatory markers. Results:Among 106 participants who satisfied the trial entrance criteria, 27% ( n = 15) and 12% ( n = 6) of patients in the high-protein versus low-protein hemodialysis meal groups, respectively, achieved the primary outcome (intention-to-treat P-value = 0.045). A lower proportion of patients in the high-protein versus low-protein intake groups experienced a meaningful rise in interleukin-6 levels: 9% versus 31%, respectively (P = 0.009). No serious adverse events were observed. Conclusion:In hypoalbuminemic hemodialysis patients, high-protein meals during dialysis combined with lanthanum carbonate are safe and increase serum albumin while controlling phosphorus.

Project description:BACKGROUND AND OBJECTIVES:Epidemiologic studies suggest that higher serum phosphaturic hormone fibroblast growth factor 23 levels are associated with increase morbidity and mortality. The aim of the FGF23 Reduction Efficacy of a New Phosphate Binder in CKD Trial was to evaluate the effect of sevelamer carbonate on serum C-terminal fibroblast growth factor 23 levels in normophosphatemic patients with CKD stage 3b/4. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Patients with CKD, eGFR between 45 and 15 ml/min per 1.73 m2, fasting serum phosphate concentration >3.1 mg/dl, and serum C-terminal fibroblast growth factor 23 >80 relative units/ml were included in our double-blind, placebo-controlled, randomized multicenter study. All patients received 100,000 IU cholecalciferol at time of randomization. Participants received either placebo or sevelamer carbonate 4.8 g daily during a 12-week period. Biologic parameters, including serum C-terminal fibroblast growth factor 23, intact fibroblast growth factor 23, and ?-klotho, were evaluated at baseline and 12 weeks after inclusion. RESULTS:Of 96 screened patients, 78 (mean±SD age: 63±13 years old; 70% men; mean eGFR: 27±9 ml/min per 1.73 m2) met the inclusion criteria. At baseline, mean eGFR was 27±9 ml/min per 1.73 m2, mean serum phosphate level was 3.8±0.5 mg/dl, and median (interquartile range) serum C-terminal fibroblast growth factor 23 level was 157 (120-241) relative units/ml. After 12 weeks of treatment, urinary phosphate-to-creatinine ratio fell significantly in the sevelamer group. The sevelamer and placebo groups did not differ significantly in terms of median change in serum C-terminal fibroblast growth factor 23 levels: the median (interquartile range) change was 38 (-13-114) relative units/ml in the placebo group and 37 (-1-101) relative units/ml in the sevelamer group (P=0.77). There was no significant difference in serum intact fibroblast growth factor 23, ?-klotho, or phosphate levels changes between the two groups. Serum total and LDL cholesterol levels fell significantly in the sevelamer group. CONCLUSIONS:In our double-blind, placebo-controlled, randomized study performed in normophosphatemic patients with CKD, a 12-week course of sevelamer carbonate significantly reduced phosphaturia without changing serum phosphorus but did not significantly modify serum C-terminal fibroblast growth factor 23 and intact fibroblast growth factor 23 or ?-klotho levels.

Dataset Information

Lanthanum carbonate reduces phosphorus burden in patients with CKD stages 3 and 4: a randomized trial.

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Lanthanum carbonate reduces phosphorus burden in patients with CKD stages 3 and 4: a randomized trial.

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