Aurélie Lenglet1,2, Sophie Liabeuf1,3, Najeh El Esper4, Sandrine Brisset3, Janette Mansour5, Anne-Sophie Lemaire-Hurtel6, Aurelien Mary1,2, Michel Brazier1,7, Said Kamel1,7, Romuald Mentaverri1,7, Gabriel Choukroun1,4, Albert Fournier4, Ziad A Massy8,9,10,11. 1. INSERM U1088, Jules Verne University of Picardie, Amiens, France. 2. Pharmacy, University Hospital, Amiens, France. 3. Clinical Research Centre and Division of Clinical Pharmacology, University Hospital, Amiens, France. 4. Department of Nephrology Internal Medicine, Dialysis, Transplantation and Intensive Care, University Hospital, Amiens, France. 5. Department of Nephrology, Centre Hospitalier de Soissons, Soissons, France. 6. Laboratory of Pharmacology and Toxicology, University Hospital, Amiens, France. 7. Laboratory of Endocrine and Bone Biology, University Hospital, Amiens, France. 8. Division of Nephrology, Ambroise Paré Hospital-APHP and Paris Ile de France Ouest University (UVSQ), Boulogne-Billancourt, France. 9. Inserm U-1018, Centre de recherche en épidémiologie et santé des populations (CESP), Equipe 5, Villejuif, France. 10. Paris-Sud University (PSU), Orsay, France. 11. University of Paris Ouest-Versailles-Saint-Quentin-en-Yvelines (UVSQ), Versailles, France.
Abstract
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.
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.
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Authors: Aurelie Lenglet; Nicolas Fabresse; Méline Taupin; Cathy Gomila; Sophie Liabeuf; Said Kamel; Jean Claude Alvarez; Tilman B Drueke; Ziad A Massy Journal: Drugs Date: 2019-06 Impact factor: 9.546
Authors: Sophie Liabeuf; Jean-Philippe Ryckelynck; Najeh El Esper; Pablo Ureña; Christian Combe; Bertrand Dussol; Denis Fouque; Philippe Vanhille; Luc Frimat; Eric Thervet; Romuald Mentaverri; Dominique Prié; Gabriel Choukroun Journal: Clin J Am Soc Nephrol Date: 2017-10-26 Impact factor: 8.237