To compare the reduction of serum phosphorus (PO4) with lanthanum carbonate (LC) and sevelamer hydrochloride (SH)
Study design and study population:
This was an open-label, randomized, multi-centre crossover study in patients on hemodialysis.
Intervention or observation
Following a 2-3 week washout period, 182 patients with serum PO4 >1.92mmol/L and corrected calcium > 2.18 were randomized (1:1) to receive LC (dose titrated from 2250mg to 3000mg/day) or SH (dose titrated from 4800mg to 6400mg/day) for 4 weeks. Patients underwent a second washout period of 2 weeks and then switched to the alternative binder for 4 weeks. Patients with an iPTH > 66pmol/L were excluded from the study.
Cinacalcet and compounds containing PO4, Mg, Aluminum or Calcium (as a phosphate binder) were not allowed during the study. Patients were instructed to maintain a consistent diet with phosphorous and protein. Night-time calcium supplementation was allowed during washout to prevent hypocalcemia. Doses of vitamin D analogues and calcium were to remain stable after randomization.
Primary End point, Secondary Endpoint
Primary End Point: Change from baseline in serum PO4 at the end of each treatment period (ITT).
Secondary Endpoint: Change from baseline in serum PO4 at the end of each treatment period (completers- defined as all patients who completed 4 wks of treatment of both binders and had a valid serum PO4 measurement at the end of each treatment period)
Other Pre-specified Endpoints
– changes in serum Ca
– changes in iPTH levels
– safety & tolerability
Shown by the ITT population, both LC and SH at the doses used in the study are efficacious at lowering serum PO4 by a clinically meaningful amount:
- LC ~ 0.55mmol/L; SH ~ 0.45mmol/L
LC lowers serum PO4 slightly better compared to SH in the “ideal” world – i.e. shown by the “Completer population” which represents patients adherent to the medication. LC lowers serum PO4 by 0.16mmol/L compared to SH. This however is not clinically significant.
- Adverse events for LC vs. SH were 44.7% vs. 50.9%. There were more GI-related adverse events reported for SH vs. LC – 23.3% vs. 18.2%
- Similar number of withdrawals due to adverse events with both agents (8 vs. 10 patients)
- Similar for both groups (25 for LC; 23 for SH)
The advantage of a crossover design is that it eliminates individual subject differences since each patient acts as their own control and thus there are less confounders. The disadvantage of a cross over design includes the persistence of the first treatment – although this study did include a reasonable washout period between treatments. Other limitations to this study include the short duration which underestimates the drop out rate. Long–term safety was not assessed which is most concerning with LC and the potential accumulation in tissues and bone. Finally a fixed-dose does not assess effectiveness of agents but only efficacy of the doses chosen.
The doses of both agents used in this study (lanthanum carbonate 3g/day and sevelamer hydrochloride 6400mg/day) would cost $12/day. Although both agents were effective in lowering phosphorous, LC required only 3 tablets/day vs. SH which required 8 tablets/day. Therefore, as both of these agents are extremely costly, the use of these agents should be reserved for patients who cannot take calcium as a phosphate binder.