Distinct Phosphate Targets Feasible, Pilot Study Shows

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A randomized controlled pilot study demonstrated the feasibility and safety of performing a large clinical trial that is powered to establish whether phosphate lowering reduces fatal and nonfatal card
A randomized controlled pilot study demonstrated the feasibility and safety of performing a large clinical trial that is powered to establish whether phosphate lowering reduces fatal and nonfatal card

Researchers have taken an important step towards a trial evaluating phosphate binders for clinically important outcomes.

In a pilot randomized controlled trial published in the Clinical Journal of the American Society of Nephrology, Ron Wald, MD, of St. Michael's Hospital in Toronto, Ontario, Canada, and colleagues reported that achieving two distinct phosphate targets is feasible and sustainable. During March to October 2014, 104 patients on conventional hemodialysis (HD) were randomly assigned to 26 weeks treatment toward an intensive phosphate target within or near normal range (2.33–4.66 mg/dL) or a liberalized target (6.20–7.75 mg/dL). The patients, from 5 HD centers in Canada, received calcium carbonate titrated up to 3 g daily using a dosing nomogram.

Over 26 weeks, the intensive group required a median 1800 mg calcium carbonate to reach their goal and the liberalized group generally none. A separation in serum phosphate between groups occurred within 2 weeks and was sustained during the trial period. More than half (54.7%) of the intensive group achieved their goal below 4.66 mg/dL, whereas only 27.5% of the liberalized group reached their target above 6.20 mg/dL.

Average phosphate at 26 weeks was 4.53 mg/dL vs 6.05 mg/dL for the intensive and liberalized groups, respectively. It declined 1.24 mg/dL more in the intensive group. That decrement “might reasonably be expected to result in important effects on survival.”

Excessive hyperphosphatemia above 7.75 mg/dL developed in 42% of the liberalized group and 3.8% of the intensive group. The investigators observed no differences in the risks for hypercalcemia, hypocalcemia, parathyroidectomy, or major vascular events. Only slightly higher calcium levels were observed in the intensive group. There were also no meaningful differences between groups in the change in parathyroid hormone levels, dialysate calcium prescription, or dose of activated vitamin D analogs. In addition, patients from both groups reported similar health-related quality of life.

“Although this pilot trial was not intended to examine the effect of phosphate lowering on patient-important events, it demonstrates the feasibility and safety of performing a large clinical trial, powered to establish whether phosphate lowering reduces fatal and nonfatal cardiovascular events,” Dr Wald and the team wrote.

“This study shows that distinct phosphate targets are feasible and provides hope for these definitive studies,” Robert E. Olivo, MD, and Julia J. Scialla, MD, commented in an accompanying editorial. “The nephrology community should strongly support efforts to develop evidence for phosphate management by conducting appropriately powered outcomes trials.”

References

Wald R, Rabbat CG, Girard L, et al. Two phosphAte taRGets in End-stage renal disease Trial (TARGET): A Randomized Controlled Trial. Clin J Am Soc Nephrol 2017;12:965–973. doi: 10.2215/CJN.10941016

Olivo RE and Scialla JJ. Getting out of the phosphate bind: Trials to guide treatment targets. Clin J Am Soc Nephrol 2017;12: 868–870. doi: 10.2215/CJN.04380417

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