Nicotinamide combined with phosphate binders improves hyperphosphatemia and calcification propensity in patients on hemodialysis (HD), according to new study findings.

In a double-blind, randomized controlled trial (EudraCT Number 2013-000488-95), investigators assigned 539 patients with serum phosphate levels of 4.5 mg/dL or greater despite phosphate binder use to receive nicotinamide modified release (250-1500 mg/d) and 183 patients to receive placebo, along with 1 to 2 phosphate binders. Some patients with secondary hyperparathyroidism also received active vitamin D analogues and calcimimetics.

After 12 weeks, serum phosphate concentration was a significant 0.51 mg/dL lower in the nicotinamide than placebo group: 5.36 vs 5.88 mg/dL, Richard Ammer, MD, of Universitätsklinikum Münster in Germany, and colleagues reported in Kidney International Reports. Further, more nicotinamide recipients achieved target range serum phosphate (31.5% vs 20.8%). They had a significant 78% and 28% higher likelihood of achieving serum phosphate levels of 4.5 mg/dL or less or 5.5 mg/dL or less, respectively, compared with patients receiving placebo. Concurrently, intact parathyroid hormone (iPTH) declined significantly by 21.9 pg/mL in the nicotinamide group to 292.4 pg/mL over 12 weeks, whereas it increased by 28.5 pg/mL to 337.0 pg/mL in the placebo group.

Notably, the investigators found that nicotinamide treatment significantly prolonged T50 time, a measure of calcification propensity, compared with placebo: 23.8 vs 2.3 minutes, “indicating a relevant biological and potentially vasculoprotective effect of the intervention.”


Continue Reading

With respect to adverse events, more patients taking nicotinamide experienced diarrhea (30.7% vs 12.6%) and pruritus (9.8% vs 2.7%). Platelet count also was significantly lower in the nicotinamide group (194.1 vs 209.0 per nL) after 12 weeks of treatment but resolved with medication cessation.

Use of phosphate binders results in upregulation of the sodium-dependent phosphate cotransporter 2b, but it may be prevented by coadministration of nicotinamide, Dr Ammer’s team explained.

The investigators concluded that  “the results of this phase III study prove the phosphate-lowering potential of [nicotinamide modified release] as an add-on therapeutic approach to established, but insufficiently effective, [phosphate binder] therapy in hemodialysis patients. They also show that the additional phosphate reduction achieved may be associated with favorable changes of other CKD-MBD parameters.”

Disclosure: This clinical trial was supported by MEDICE Medicines Pütter GmbH & Co. KG. Please see the original reference for a full list of authors’ disclosures.

Reference

Ketteler M, Wiecek A, Rosenkranz AR, et al. Efficacy and safety of a novel nicotinamide modified-release formulation in the treatment of refractory hyperphosphatemia in patients receiving hemodialysis—a randomized clinical trial. Kidney Int Rep. 6(3):594-604. doi:10.1016/j.ekir.2020.12.012