Efficacy and safety of nicotinamide in haemodialysis patients: the NICOREN study

Background: Nicotinamide (NAM) has been proposed as an alternative treatment to phosphate binders for hyperphosphataemia in chronic kidney disease. Methods: The NICOREN multicentre, open-label and randomized study was designed to examine non-inferiority and safety of NAM when compared with sevelamer (SEV) in chronic haemodialysis patients. One hundred patients were randomized to either NAM or SEV treatment for 24 weeks. Serum biochemistry and NAM's main metabolite, N-methyl-2-pyridone-5-carboxamide (2PY), were measured to assess compliance, efficacy and safety. Results: After 24 weeks, we observed a comparable decrease in serum phosphorus in the NAM and SEV treatment arms, from 2.1 +/- 0.4 to 1.8 +/- 0.5 and 2.3 +/- 0.5 to 1.7 +/- 0.5 mM (P = not significant), respectively. The criterion for non-inferiority was, however, not met due to a more limited number of patients being included than planned. Treatment discontinuation due to adverse events was 1.6 times higher in the NAM than in the SEV group with only 55% of study completers in the NAM arm versus 90% in the SEV arm. Thrombocytopenia was observed in four NAM-treated patients. Serum 2PY levels were comparable at baseline, but increased markedly in the NAM group, but not in the SEV group, at 24 weeks (P < 0.0001). Conclusions: Thus, both drugs are equally effective in lowering serum phosphorus, but patients' tolerance of NAM was largely inferior to that of SEV. Extremely high 2PY levels may contribute to NAM's side effects.