{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T01:46:26Z","timestamp":1773798386704,"version":"3.50.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T00:00:00Z","timestamp":1656115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"MEDICE Arzneimittel P\u00fctter GmbH & Co."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>We previously reported that modified-release nicotinamide (NAMR) was superior to placebo in reducing serum phosphate concentrations over 12 weeks in a large cohort of haemodialysis patients with hyperphosphataemia. Here we report outcomes after 52 weeks of treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>NOPHOS was a phase 3, international, randomized, controlled, double-blind trial with a parallel group design. NAMR (250\u20131500\u00a0mg\/day) was investigated in comparison to placebo as an add-on therapy to an individual therapy with approved phosphate binders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the intention-to-treat population (NAMR: n\u00a0=\u00a0539; placebo: n\u00a0=\u00a0183), serum phosphate was significantly lower in the NAMR group compared with the placebo group at week 24 (5.40\u00a0\u00b1\u00a01.55\u00a0versus 5.79\u00a0\u00b1\u00a01.37\u00a0mg\/dl, P\u00a0&amp;lt;\u00a0.001) with a mean difference of \u22120.39\u00a0mg\/dl [95% confidence interval (CI) \u22120.66 to \u22120.13], but was comparable between the groups at week 52 [mean difference \u22120.08 (95% CI \u22120.36\u20130.20)]. In the completer population (n\u00a0=\u00a0358), statistical significance in favour of NAMR was reached at weeks 24 and 52. The treatment effect was reduced in patients with high baseline serum intact parathyroid hormone (iPTH) compared with patients with low baseline serum iPTH. Compliant patients in the NAMR group had a more pronounced and sustained reduction in serum phosphate than non-compliant patients. NAMR treatment was associated with a significantly increased risk of thrombocytopenia, pruritus, anaemia, and diarrhoea. Herpes zoster occurred exclusively in patients randomized to NAMR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NAMR combined with phosphate binders significantly reduced serum phosphate over the first 24 weeks of treatment, but the treatment effect was not maintained up to week 52. Non-compliance may have contributed to reduced long-term efficacy. Several newly identified safety signals warrant further evaluation.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ndt\/gfac206","type":"journal-article","created":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T13:41:31Z","timestamp":1656164491000},"page":"982-991","source":"Crossref","is-referenced-by-count":9,"title":["Modified-release nicotinamide for the treatment of hyperphosphataemia in haemodialysis patients: 52-week efficacy and safety results of the phase 3 randomized controlled NOPHOS trial"],"prefix":"10.1093","volume":"38","author":[{"given":"Markus","family":"Ketteler","sequence":"first","affiliation":[{"name":"Department of General Internal Medicine and Nephrology, Robert Bosch Hospital, Stuttgart , Germany"},{"name":"School of Medicine, University of Split , Split , Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrzej","family":"Wiecek","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice , Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander R","family":"Rosenkranz","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Medical University of Graz , Graz , Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Ose","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen , Essen , Germany"},{"name":"Center for Clinical Trials, University Hospital Essen, University of Duisburg-Essen , Essen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Rekowski","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen , Essen , Germany"},{"name":"Center for Clinical Trials, University Hospital Essen, University of Duisburg-Essen , Essen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Horst","family":"Lorenz","sequence":"additional","affiliation":[{"name":"B\u00fcro f\u00fcr Biometrie und Statistik , Neuberg , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Burkhard","family":"Hellmann","sequence":"additional","affiliation":[{"name":"Medical Department, MEDICE Arzneimittel P\u00fctter GmbH & Co. KG , Iserlohn , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Karus","sequence":"additional","affiliation":[{"name":"Medical Department, MEDICE Arzneimittel P\u00fctter GmbH & Co. KG , Iserlohn , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela","family":"Ruhmann","sequence":"additional","affiliation":[{"name":"Medical Department, MEDICE Arzneimittel P\u00fctter GmbH & Co. KG , Iserlohn , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Ammer","sequence":"additional","affiliation":[{"name":"Medical Department, MEDICE Arzneimittel P\u00fctter GmbH & Co. KG , Iserlohn , Germany"},{"name":"Department of Nephrology, University Hospital M\u00fcnster , M\u00fcnster , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,6,25]]},"reference":[{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1097\/01.ASN.0000133041.27682.A2","article-title":"Mineral metabolism, mortality, and morbidity in maintenance hemodialysis","volume":"15","author":"Block","year":"2004","journal-title":"J Am Soc Nephrol"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/sj.ki.5001514","article-title":"Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients","volume":"70","author":"Kalantar-Zadeh","year":"2006","journal-title":"Kidney Int"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1093\/ndt\/gfq219","article-title":"Serum iPTH, calcium and phosphate, and the risk of mortality in a European haemodialysis population","volume":"26","author":"Floege","year":"2011","journal-title":"Nephrol Dial Transplant"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1053\/j.ajkd.2008.03.020","article-title":"Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS)","volume":"52","author":"Tentori","year":"2008","journal-title":"Am J Kidney Dis"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1744-9987.2007.00540.x","article-title":"Effects of serum calcium, phosphorous, and intact parathyroid hormone levels on survival in chronic hemodialysis patients in Japan","volume":"12","author":"Nakai","year":"2008","journal-title":"Ther Apher Dial"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1093\/ndt\/gfv099","article-title":"Improvement of mineral and bone metabolism markers is associated with better survival in haemodialysis patients: the COSMOS Study","volume":"30","author":"Fernandez-Martin","year":"2015","journal-title":"Nephrol Dial Transplant"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.cca.2017.09.005","article-title":"Phosphorus and mortality risk in end-stage renal disease: a meta-analysis","volume":"474","author":"Hou","year":"2017","journal-title":"Clin Chim Acta"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.kisu.2017.04.001","article-title":"KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD)","volume":"7","author":"Kidney Disease: Improving Global Outcomes CKD-MBD Update Work Group","year":"2017","journal-title":"Kidney Int"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1093\/ndt\/gfs418","article-title":"COSMOS: the dialysis scenario of CKD-MBD in Europe","volume":"28","author":"Fernandez-Martin","year":"2013","journal-title":"Nephrol Dial Transplant"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1007\/s40265-018-0950-2","article-title":"Targeting gastrointestinal transport proteins to control hyperphosphatemia in chronic kidney disease","volume":"78","author":"Fouque","year":"2018","journal-title":"Drugs"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1681\/ASN.2009050559","article-title":"Intestinal Npt2b plays a major role in phosphate absorption and homeostasis","volume":"20","author":"Sabbagh","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1093\/ndt\/gfaa156","article-title":"Evidence of an intestinal phosphate transporter alternative to type IIb sodium-dependent phosphate transporter in rats with chronic kidney disease","volume":"36","author":"Ichida","year":"2021","journal-title":"Nephrol Dial Transplant"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.kint.2020.02.040","article-title":"EOS789, a novel pan-phosphate transporter inhibitor, is effective for the treatment of chronic kidney disease-mineral bone disorder","volume":"98","author":"Tsuboi","year":"2020","journal-title":"Kidney Int"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1093\/ndt\/14.5.1195","article-title":"Nicotinamide inhibits sodium-dependent phosphate cotransport activity in rat small intestine","volume":"14","author":"Katai","year":"1999","journal-title":"Nephrol Dial Transplant"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1093\/ndt\/gfh781","article-title":"Nicotinamide prevents the development of hyperphosphataemia by suppressing intestinal sodium-dependent phosphate transporter in rats with adenine-induced renal failure","volume":"20","author":"Eto","year":"2005","journal-title":"Nephrol Dial Transplant"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1111\/j.1523-1755.2004.00482.x","article-title":"Nicotinamide suppresses hyperphosphatemia in hemodialysis patients","volume":"65","author":"Takahashi","year":"2004","journal-title":"Kidney Int"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.2215\/CJN.04211007","article-title":"A randomized, double-blind, placebo-controlled trial of niacinamide for reduction of phosphorus in hemodialysis patients","volume":"3","author":"Cheng","year":"2008","journal-title":"Clin J Am Soc Nephrol"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1177\/089686080902900515","article-title":"The effect of oral niacinamide on plasma phosphorus levels in peritoneal dialysis patients","volume":"29","author":"Young","year":"2009","journal-title":"Perit Dial Int"},{"key":"2023033113235377700_","first-page":"58","article-title":"Oral nicotinamide reduces serum phosphorus, increases HDL, and induces thrombocytopenia in hemodialysis patients: a double-blind randomized clinical trial","volume":"31","author":"Shahbazian","year":"2011","journal-title":"Nefrologia"},{"key":"2023033113235377700_","first-page":"1","article-title":"The effect of coadminstration of nicotinamide and calcium-based phosphate binder on hyperphosphatemia in patients undergoing hemodialysis","volume":"5","author":"Allam","year":"2012","journal-title":"Adv Nat Sci"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s00467-015-3208-1","article-title":"Efficacy and safety of nicotinamide in the management of hyperphosphatemia in pediatric patients on regular hemodialysis","volume":"31","author":"El Borolossy","year":"2016","journal-title":"Pediatr Nephrol"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1093\/ndt\/gfx249","article-title":"Efficacy and safety of nicotinamide in haemodialysis patients: the NICOREN Study","volume":"32","author":"Lenglet","year":"2017","journal-title":"Nephrol Dial Transplant"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"530","DOI":"10.21037\/atm.2020.03.228","article-title":"Investigation of nicotinamide as more than an anti-phosphorus drug in chronic hemodialysis patients: a single-center, double-blind, randomized, placebo-controlled trial","volume":"8","author":"Liu","year":"2020","journal-title":"Ann Transl Med"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.ekir.2020.12.012","article-title":"Efficacy and safety of a novel nicotinamide modified-release formulation in the treatment of refractory hyperphosphatemia in patients receiving hemodialysis\u2014a randomized clinical trial","volume":"6","author":"Ketteler","year":"2021","journal-title":"Kidney Int Rep"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1214\/aos\/1176345976","article-title":"Cox's regression model for counting processes: a large sample study","volume":"10","author":"Andersen","year":"1982","journal-title":"Ann Stat"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/pst.1757","article-title":"Safety data from randomized controlled trials: applying models for recurrent events","volume":"15","author":"Hengelbrock","year":"2016","journal-title":"Pharm Stat"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"e0144119","DOI":"10.1371\/journal.pone.0144119","article-title":"Nonadherence to medication therapy in haemodialysis patients: a systematic review","volume":"10","author":"Ghimire","year":"2015","journal-title":"PLoS One"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1471-2369-9-2","article-title":"A systematic review of the prevalence and determinants of nonadherence to phosphate binding medication in patients with end-stage renal disease","volume":"9","author":"Karamanidou","year":"2008","journal-title":"BMC Nephrol"},{"key":"2023033113235377700_","first-page":"525","article-title":"Challenge of phosphorus control in hemodialysis patients: a problem of adherence?","volume":"23","author":"Arenas","year":"2010","journal-title":"J Nephrol"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/hdi.12315","article-title":"Phosphate binder pill burden, patient-reported non-adherence, and mineral bone disorder markers: findings from the DOPPS","volume":"20","author":"Fissell","year":"2016","journal-title":"Hemodial Int"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/ki.2008.130","article-title":"Hyperphosphatemia of chronic kidney disease","volume":"74","author":"Hruska","year":"2008","journal-title":"Kidney Int"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1038\/sj.ki.5000381","article-title":"Diarrhea induced by high doses of nicotinamide in dialysis patients","volume":"69","author":"Delanaye","year":"2006","journal-title":"Kidney Int"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1111\/j.1523-1755.2005.00583_8.x","article-title":"Thrombocytopenia induced by nicotinamide in hemodialysis patients","volume":"68","author":"Rottembourg","year":"2005","journal-title":"Kidney Int"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1056\/NEJMc1311039","article-title":"Safety profile of extended-release niacin in the AIM-HIGH trial","volume":"371","author":"Anderson","year":"2014","journal-title":"N Engl J Med"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1097\/00005792-197211000-00002","article-title":"Constitutional hepatic dysfunction (CHD; Gilbert's disease); a review with special reference to a characteristic increase and prolongation of the hyperbilirubinemic response to nicotinic acid","volume":"51","author":"Fromke","year":"1972","journal-title":"Medicine (Baltimore)"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1007\/BF01314468","article-title":"Studies on nicotinic acid interaction with bilirubin metabolism","volume":"24","author":"Ohkubo","year":"1979","journal-title":"Dig Dis Sci"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1161\/CIRCULATIONAHA.111.053108","article-title":"Niacin inhibits vascular inflammation via the induction of heme oxygenase-1","volume":"125","author":"Wu","year":"2012","journal-title":"Circulation"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1053\/j.ajkd.2011.10.049","article-title":"Risk of herpes zoster in patients treated with long-term hemodialysis: a matched cohort study","volume":"59","author":"Kuo","year":"2012","journal-title":"Am J Kidney Dis"},{"key":"2023033113235377700_","first-page":"263","article-title":"End-stage renal disease (ESRD) contributes to the increasing prevalence of herpes zoster","volume":"2","author":"Sato","year":"2009","journal-title":"NDT Plus"},{"key":"2023033113235377700_","first-page":"462","article-title":"Effectiveness of herpes zoster vaccine in patients 60 years and older with end-stage renal disease","volume":"62","author":"Tseng","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.puhe.2018.10.015","article-title":"Systematic review of the evidence on the epidemiology of herpes zoster: incidence in the general population and specific subpopulations in Spain","volume":"167","author":"Mareque","year":"2019","journal-title":"Public Health"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s13300-018-0394-4","article-title":"Herpes zoster and diabetes mellitus: a review","volume":"9","author":"Papagianni","year":"2018","journal-title":"Diabetes Ther"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s12879-018-3121-x","article-title":"Risk and impact of herpes zoster among COPD patients: a population-based study, 2009-2014","volume":"18","author":"Munoz-Quiles","year":"2018","journal-title":"BMC Infect Dis"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1056\/NEJMoa1300955","article-title":"Effects of extended-release niacin with laropiprant in high-risk patients","volume":"371","author":"HPS2-THRIVE Collaborative Group","year":"2014","journal-title":"N Engl J Med"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"245","DOI":"10.4103\/0971-4065.83735","article-title":"Safety and efficacy of nicotinamide in the management of hyperphosphatemia in patients on hemodialysis","volume":"21","author":"Vasantha","year":"2011","journal-title":"Indian J Nephrol"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1001\/archinte.162.14.1568","article-title":"Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes: results of the assessment of diabetes control and evaluation of the efficacy of niaspan trial","volume":"162","author":"Grundy","year":"2002","journal-title":"Arch Intern Med"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1111\/j.1742-1241.2008.01938.x","article-title":"Lipid-modifying efficacy and tolerability of extended-release niacin\/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia","volume":"62","author":"Maccubbin","year":"2008","journal-title":"Int J Clin Pract"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jacl.2010.02.002","article-title":"Safety of extended-release niacin\/laropiprant in patients with dyslipidemia","volume":"4","author":"McKenney","year":"2010","journal-title":"J Clin Lipidol"},{"key":"2023033113235377700_","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1136\/heartjnl-2015-308055","article-title":"Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomised controlled trials","volume":"102","author":"Goldie","year":"2016","journal-title":"Heart"}],"container-title":["Nephrology Dialysis Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ndt\/advance-article-pdf\/doi\/10.1093\/ndt\/gfac206\/45291884\/gfac206.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ndt\/article-pdf\/38\/4\/982\/49715359\/gfac206.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ndt\/article-pdf\/38\/4\/982\/49715359\/gfac206.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T19:03:47Z","timestamp":1700766227000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ndt\/article\/38\/4\/982\/6617886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,25]]},"references-count":49,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,6,25]]},"published-print":{"date-parts":[[2023,3,31]]}},"URL":"https:\/\/doi.org\/10.1093\/ndt\/gfac206","relation":{},"ISSN":["0931-0509","1460-2385"],"issn-type":[{"value":"0931-0509","type":"print"},{"value":"1460-2385","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,4]]},"published":{"date-parts":[[2022,6,25]]}}}