ISTANBUL, Turkey — For hemodialysis-dependent patients with chronic kidney disease, soluble ferric pyrophosphate is as safe as other iron replacements and reduces the need for erythropoiesis-stimulating agents by 35%, according to a double-blind placebo-controlled trial.

In patients who received soluble ferric pyrophosphate, hemoglobin levels were maintained and there was no evidence of iron overload.

Hemodialysis patients routinely lose blood during the procedure, and can require iron replacement therapy and erythropoiesis-stimulating agents, such as erythropoietin. However, these agents have drawbacks. "Erythropoietin is associated with increased cardiovascular morbidity and mortality, and is a very expensive drug," said Ajay Gupta, MD, chief scientific officer at Rockwell Medical in Wixom, Michigan.

Dr. Gupta reported the study results during a news conference here at the European Renal Association-European Dialysis and Transplant Association 50th Congress.

Soluble ferric pyrophosphate is a novel iron compound that binds to apotransferrin and is delivered to the hemodialysis patient in the dialysate.

To evaluate its use in hemodialysis patients, Dr. Gupta and his team conducted the Continuous Soluble Ferric Pyrophosphate Iron Delivery Via Dialysate in Hemodialysis Patients (PRIME) study. They looked at the effect of soluble ferric pyrophosphate on the dose of erythropoiesis-stimulating agent required to maintain hemoglobin levels in a target range of 9.5 to 11.5 g/L.

Of the 103 study subjects, they randomized 52 to receive soluble ferric pyrophosphate 2 μmol/L in dialysate (110 μg iron/L of dialysate) and 51 to standard dialysate. The study was conducted over a 36-week period. A centralized anemia management center controlled prescriptions for erythropoiesis-stimulating agents to ensure consistent adherence to the hemoglobin target range.

Inclusion criteria were hemoglobin levels between 9.5 and 12.0 g/dL, stable dosing levels of erythropoiesis-stimulating agents, transferrin saturation between 15% and 40%, and ferritin levels between 200 and 1000 μg/L.

Exclusion criteria were hemodialysis conducted by catheter vascular access, intravenous administration of more than 600 mg iron in the 6 weeks preceding enrollment, and unstable dosing regimens of erythropoiesis-stimulating agents.

The researchers found that the mean change from baseline in the dose of erythropoiesis-stimulating agents was lower in the soluble ferric pyrophosphate group than in the placebo group (4.9% vs 39.8%).

Table. PRIME Study Mean Change From Baseline

Parameter Baseline Levels in Soluble Ferric Pyrophosphate Group Change From Baseline in Soluble Ferric Pyrophosphate Group (n = 52) Baseline Levels in Placebo Group Change From Baseline in Placebo Group (n = 51)
Hemoglobin (g/mL) 109.6 –5.0 111.1 –7.1
Ferritin (μg/L) 621.5 –61.9 604.9 –156
Epoetin dose (units/week) 9483 +388 9206 +3423

 

Overall, adverse events were similar with soluble ferric pyrophosphate and placebo (92.6% vs 93.9%). Adverse events were typical of what is seen in hemodialysis-dependent patients with chronic kidney disease, according to the researchers.

"Soluble ferric pyrophosphate significantly reduces the need for erythropoiesis-stimulating agents and intravenous iron agents without an intravenous iron source. It appears very safe," said Dr. Gupta.

There is still more work to be done, said Ziad Massy, MD, professor of nephrology at Ambroise Paré Hospital in Paris, France, who attended the session.

"Depending on how much iron you deliver and how fast you deliver it, the concern is always that you can increase oxidative stress. We need more data on the safety of this delivery method, especially for oxidative stress markers," Dr. Massy told Medscape Medical News. However, he acknowledged, "Dr. Gupta said he is going to do it."

This study was funded by Rockwell Medical. Dr. Gupta invented soluble ferric pyrophosphate and licensed it to Rockwell Medical, where he is chief scientific officer. Dr. Massy reports receiving research funding from Baxter and Fresenius Medical Care.

European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) 50th Congress. Presented May 19, 2013.

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