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Efficacy and Safety of a Novel Nicotinamide Modified-Release Formulation in the Treatment of Refractory Hyperphosphatemia in Patients Receiving Hemodialysis—A Randomized Clinical Trial

INTRODUCTION: Despite widespread use of phosphate binders (PBs), phosphate control is insufficient in many hemodialysis patients. Preliminary clinical observations suggest that nicotinamide may act synergistically with PBs to improve phosphate control. METHODS: This multinational, randomized, double...

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Autores principales: Ketteler, Markus, Wiecek, Andrzej, Rosenkranz, Alexander R., Pasch, Andreas, Rekowski, Jan, Hellmann, Burkhard, Karus, Michael, Ammer, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938065/
https://www.ncbi.nlm.nih.gov/pubmed/33732974
http://dx.doi.org/10.1016/j.ekir.2020.12.012
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author Ketteler, Markus
Wiecek, Andrzej
Rosenkranz, Alexander R.
Pasch, Andreas
Rekowski, Jan
Hellmann, Burkhard
Karus, Michael
Ammer, Richard
author_facet Ketteler, Markus
Wiecek, Andrzej
Rosenkranz, Alexander R.
Pasch, Andreas
Rekowski, Jan
Hellmann, Burkhard
Karus, Michael
Ammer, Richard
author_sort Ketteler, Markus
collection PubMed
description INTRODUCTION: Despite widespread use of phosphate binders (PBs), phosphate control is insufficient in many hemodialysis patients. Preliminary clinical observations suggest that nicotinamide may act synergistically with PBs to improve phosphate control. METHODS: This multinational, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of nicotinamide modified release (NAMR) in combination with oral PB in a large cohort of hemodialysis patients with abnormal serum phosphate concentration (>4.5 mg/dl) despite treatment with PB. Patients entered a proof-of-efficacy phase (12 weeks [W12]) in which adjustments of relevant comedication were not permitted, followed by a safety extension phase for up to 52 weeks. Here, we report the results of the first phase. RESULTS: The intention-to-treat (ITT) population consisted of 539 patients in the NAMR and 183 patients in the placebo group. NAMR and placebo were orally administered once daily (250–1500 mg/d). Mean age of patients was 61.8 years, and 63.0% were men. In the confirmatory analysis that estimated the difference in serum phosphate concentration after 12 weeks, NAMR proved superior over placebo with a significant difference of –0.51 mg/dl (95% confidence interval [CI] –0.72, –0.29; P < 0.0001). This effect was associated with significantly lower intact parathyroid hormone (iPTH) values (NAMR: 292.4±300.4 pg/ml vs. placebo: 337.0±302.7 pg/ml; P = 0.04) and an improved calcification propensity (T50 time; NAMR: 23.8±97.1 minutes vs. placebo: 2.3±100.7 minutes; P = 0.02). Diarrhea and pruritus were more frequent in the NAMR group. CONCLUSION: NAMR combined with oral PB significantly improved phosphate control in hemodialysis patients.
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spelling pubmed-79380652021-03-16 Efficacy and Safety of a Novel Nicotinamide Modified-Release Formulation in the Treatment of Refractory Hyperphosphatemia in Patients Receiving Hemodialysis—A Randomized Clinical Trial Ketteler, Markus Wiecek, Andrzej Rosenkranz, Alexander R. Pasch, Andreas Rekowski, Jan Hellmann, Burkhard Karus, Michael Ammer, Richard Kidney Int Rep Clinical Research INTRODUCTION: Despite widespread use of phosphate binders (PBs), phosphate control is insufficient in many hemodialysis patients. Preliminary clinical observations suggest that nicotinamide may act synergistically with PBs to improve phosphate control. METHODS: This multinational, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of nicotinamide modified release (NAMR) in combination with oral PB in a large cohort of hemodialysis patients with abnormal serum phosphate concentration (>4.5 mg/dl) despite treatment with PB. Patients entered a proof-of-efficacy phase (12 weeks [W12]) in which adjustments of relevant comedication were not permitted, followed by a safety extension phase for up to 52 weeks. Here, we report the results of the first phase. RESULTS: The intention-to-treat (ITT) population consisted of 539 patients in the NAMR and 183 patients in the placebo group. NAMR and placebo were orally administered once daily (250–1500 mg/d). Mean age of patients was 61.8 years, and 63.0% were men. In the confirmatory analysis that estimated the difference in serum phosphate concentration after 12 weeks, NAMR proved superior over placebo with a significant difference of –0.51 mg/dl (95% confidence interval [CI] –0.72, –0.29; P < 0.0001). This effect was associated with significantly lower intact parathyroid hormone (iPTH) values (NAMR: 292.4±300.4 pg/ml vs. placebo: 337.0±302.7 pg/ml; P = 0.04) and an improved calcification propensity (T50 time; NAMR: 23.8±97.1 minutes vs. placebo: 2.3±100.7 minutes; P = 0.02). Diarrhea and pruritus were more frequent in the NAMR group. CONCLUSION: NAMR combined with oral PB significantly improved phosphate control in hemodialysis patients. Elsevier 2020-12-19 /pmc/articles/PMC7938065/ /pubmed/33732974 http://dx.doi.org/10.1016/j.ekir.2020.12.012 Text en © 2021 Published by Elsevier, Inc., on behalf of the International Society of Nephrology. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Clinical Research
Ketteler, Markus
Wiecek, Andrzej
Rosenkranz, Alexander R.
Pasch, Andreas
Rekowski, Jan
Hellmann, Burkhard
Karus, Michael
Ammer, Richard
Efficacy and Safety of a Novel Nicotinamide Modified-Release Formulation in the Treatment of Refractory Hyperphosphatemia in Patients Receiving Hemodialysis—A Randomized Clinical Trial
title Efficacy and Safety of a Novel Nicotinamide Modified-Release Formulation in the Treatment of Refractory Hyperphosphatemia in Patients Receiving Hemodialysis—A Randomized Clinical Trial
title_full Efficacy and Safety of a Novel Nicotinamide Modified-Release Formulation in the Treatment of Refractory Hyperphosphatemia in Patients Receiving Hemodialysis—A Randomized Clinical Trial
title_fullStr Efficacy and Safety of a Novel Nicotinamide Modified-Release Formulation in the Treatment of Refractory Hyperphosphatemia in Patients Receiving Hemodialysis—A Randomized Clinical Trial
title_full_unstemmed Efficacy and Safety of a Novel Nicotinamide Modified-Release Formulation in the Treatment of Refractory Hyperphosphatemia in Patients Receiving Hemodialysis—A Randomized Clinical Trial
title_short Efficacy and Safety of a Novel Nicotinamide Modified-Release Formulation in the Treatment of Refractory Hyperphosphatemia in Patients Receiving Hemodialysis—A Randomized Clinical Trial
title_sort efficacy and safety of a novel nicotinamide modified-release formulation in the treatment of refractory hyperphosphatemia in patients receiving hemodialysis—a randomized clinical trial
topic Clinical Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938065/
https://www.ncbi.nlm.nih.gov/pubmed/33732974
http://dx.doi.org/10.1016/j.ekir.2020.12.012
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