The Effect of Phosphate Lowering Using Sucroferric Oxyhydroxide (PA21) on Calcification Propensity of Serum

The Effect of Phosphate Lowering Using Sucroferric Oxyhydroxide (PA21) on Calcification Propensity of Serum

The Effect of Phosphate Lowering Using Sucroferric Oxyhydroxide (PA21) on Calcification Propensity of Serum

This is a single-center, prospective, open-label, controlled, randomized, cross-over study in 34 prevalent end-stage renal disease patients on chronic hemodialysis treatment with hyperphosphatemia.

Patients will be randomized in a 1:1 ratio to either receive low-dose (250mg/d) PA-21 followed by high-dose (2000mg/d) PA-21 (sequence A-B) or to receive high-dose PA21 followed by low-dose PA21 (sequence B-A) with washout-phases in between. An open label design with a sub-therapeutic dose of PA21 as control treatment was chosen because creating a convincing placebo for PA21 is not feasible. The study will start with two study visits on the 2nd and 3rd dialysis session of the week , where dialysis patients are still treated with standard of care to establish baseline values (duration: 0.5 weeks). Next will be an initial run-in wash-out phase, where all phosphate binders taken by the patient as standard of care treatment will be discontinued and no phosphate binders will be introduced. Consequently, there will be a PA21 treatment (high dose/low dose) phase, followed by a wash-out phase, followed by another PA21 treatment (high dose/low dose) phase, followed by a final wash-out phase. Each study phase, including wash-out phases as well as low-dose and high-dose treatment phases will be 14 days of duration. Patients will be followed up to 10.5 weeks after randomization until the last study visit of the final wash-out phase.

The primary outcome is change in the mean T50- Test values between different study phases (wash-out/treatment/control).

Inclusion Criteria: Prevalent patients (≥ 3 months on dialysis) treated with thrice weekly hemodialysis (HD) or hemodiafiltration (HDF) Hyperphosphatemia (serum phosphate > upper limit of normal within the last 3 months) or current phosphate binder use No use or constant dose of vitamin D and/or calcimimetics for ≥2 weeks Exclusion Criteria: Allergy to sucroferric oxyhydroxide (PA21), to other ingredients of Velphoro or to any iron-medication Current or history of calciphylaxis (calcific uremic arteriolopathy - CUA) parathormone >800 pg/ml Parathyreoidektomie planned or expected Significant GI or hepatic disorders Hypercalcemia (total serum calcium >2.6 mmol/l) at screening Antacids containing aluminum, calcium, magnesium or bicarbonate Oral iron treatments/supplements Pregnant and nursing (lactating) women