Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial

Simon D Roger, Carlo A Gaillard, Andreas H Bock, Fernando Carrera, Kai-Uwe Eckardt, David B Van Wyck, Maureen Cronin, Yvonne Meier, Sylvain Larroque, Iain C Macdougall, FIND-CKD Study Investigators, Simon D Roger, Alastair Gilles, Randall Faull, Nigel D Toussaint, Lawrence McMahon, Michael Suranyi, David Mudge, Brian Hutchison, Ashley Irish, Peter Kerr, Hemant Kulkarni, Grahame Elder, Margaret Jardine, Karl Lhotta, Gert Mayer, Raymond Vanholder, Bart Dirk Maes, Pieter Evenepoel, Frédéric Debelle, Michel Jadoul, Max Dratwa, Igor Macel, Milan Dunaj, Milan Kvapil, Petr Bucek, Jitka Rehorova, Ales Hruby, Václava Honová, Lada Malanova, Martin Lucak, Dalibor Lecian, Martin Jirovec, Jiri Vlasak, Ivan Rychlik, Stanislav Surel, Anne-Lise Kamper, Ove Ostergaard, Gudrun K Steffensen, Leila Chenine, Gabrial Choukroun, Philippe Zaoui, Christoph Wanner, Wolfgang Backs, Uwe Kraatz, Frank Dellanna, Klaus Busch, Tobias Marsen, Wolfgang Seeger, Rainer Woitas, Nicholas Obermueller, Thomas Haak, Stephan Lueders, Frank Pistrosch, Eckhard Mueller, Peter R Mertens, Werner Sutermer, Scott-Oliver Grebe, Syrus Hafezi-Rachti, Silke Roeser, Dimitrios Tsakiris, Dimitrios Memmos, Demetrios Vlachakos, Vassilis Vargemezis, Ioannis Stefanidis, Christos Syrganis, Polichronis Alivanis, Ioannis Papadakis, Nickolaos Papagalanis, Aimilios Andrikos, Dimitrios Goumenos, Kostas Siamopoulos, Charikelia Gouva, Gabriel Papadakis, Ioannis Boletis, Myrsini Tsimnadi-Spanoudaki, Dimitrios Stamatiades, Kyriaki Stamatelou, Spyridon Moutafis, Francesco Locatelli, Antonio Santoro, Francesco Quarello, Giuseppe Remuzzi, Salvatore Coppola, Rosella Ferraro Mortellaro, Andrea Icardi, Giacomo Colussi, Franco Della Grotta, Luigi Lombardi, Maurizio Gallieni, Giuseppe Villa, Giuseppe Grandaliano, Carlo Gaillard, Sebastiaan Huisman, Jos Barendregt, Peter Jh Smak Gregoor, Cecilia Oien, Boleslaw Rutkowski, Robert Malecki, Michal Nowicki, Przemyslaw Rutkowski, Kryzsztof Marczewski, Michal Mysliwiec, Antoni Sydor, Jacek Rysz, Andrzej Rydzewski, Marian Klinger, Rafal Wnuk, Piotr Kozminski, Anna Nocon, Kazimierz Ciechanowski, Pedro Correia, Fernando Neves, José Barata, Gabriel Mircescu, Mihai Voiculescu, Gheorghe Gluhovschi, Eugen Mota, Angel Luís Martín De Francisco, Alberto Torre, Alba Herreros, José Luño, E Gruss, Judith Martins, Marti Vallés, Julio Pascual, Peter Bárány, Andreas H Bock, Patrice M Ambuehl, Sehsuvar Erturk, Mustafa Arici, Saime Paydas, Zeki Soypacaci, Taner Camsari, Sedat Ustundag, Iain C Macdougall, Mark E Thomas, Richard J D'Souza, Jo E Taylor, Nicholas R Pritchard, Robin Jeffery, Stephen G Riley, Deepak Bhatnagar, Sunil Bhandari, David Reaich, Paul E Stevens, Mohsen El Kossi, Simon Roe, Brian Camilleri, Aimun Ahmed, Arif Khwaja, Barbara Thompson, Debasish Banerjee, Johann Nicholas, Alastair Hutchison, Richard Borrows, Simon D Roger, Carlo A Gaillard, Andreas H Bock, Fernando Carrera, Kai-Uwe Eckardt, David B Van Wyck, Maureen Cronin, Yvonne Meier, Sylvain Larroque, Iain C Macdougall, FIND-CKD Study Investigators, Simon D Roger, Alastair Gilles, Randall Faull, Nigel D Toussaint, Lawrence McMahon, Michael Suranyi, David Mudge, Brian Hutchison, Ashley Irish, Peter Kerr, Hemant Kulkarni, Grahame Elder, Margaret Jardine, Karl Lhotta, Gert Mayer, Raymond Vanholder, Bart Dirk Maes, Pieter Evenepoel, Frédéric Debelle, Michel Jadoul, Max Dratwa, Igor Macel, Milan Dunaj, Milan Kvapil, Petr Bucek, Jitka Rehorova, Ales Hruby, Václava Honová, Lada Malanova, Martin Lucak, Dalibor Lecian, Martin Jirovec, Jiri Vlasak, Ivan Rychlik, Stanislav Surel, Anne-Lise Kamper, Ove Ostergaard, Gudrun K Steffensen, Leila Chenine, Gabrial Choukroun, Philippe Zaoui, Christoph Wanner, Wolfgang Backs, Uwe Kraatz, Frank Dellanna, Klaus Busch, Tobias Marsen, Wolfgang Seeger, Rainer Woitas, Nicholas Obermueller, Thomas Haak, Stephan Lueders, Frank Pistrosch, Eckhard Mueller, Peter R Mertens, Werner Sutermer, Scott-Oliver Grebe, Syrus Hafezi-Rachti, Silke Roeser, Dimitrios Tsakiris, Dimitrios Memmos, Demetrios Vlachakos, Vassilis Vargemezis, Ioannis Stefanidis, Christos Syrganis, Polichronis Alivanis, Ioannis Papadakis, Nickolaos Papagalanis, Aimilios Andrikos, Dimitrios Goumenos, Kostas Siamopoulos, Charikelia Gouva, Gabriel Papadakis, Ioannis Boletis, Myrsini Tsimnadi-Spanoudaki, Dimitrios Stamatiades, Kyriaki Stamatelou, Spyridon Moutafis, Francesco Locatelli, Antonio Santoro, Francesco Quarello, Giuseppe Remuzzi, Salvatore Coppola, Rosella Ferraro Mortellaro, Andrea Icardi, Giacomo Colussi, Franco Della Grotta, Luigi Lombardi, Maurizio Gallieni, Giuseppe Villa, Giuseppe Grandaliano, Carlo Gaillard, Sebastiaan Huisman, Jos Barendregt, Peter Jh Smak Gregoor, Cecilia Oien, Boleslaw Rutkowski, Robert Malecki, Michal Nowicki, Przemyslaw Rutkowski, Kryzsztof Marczewski, Michal Mysliwiec, Antoni Sydor, Jacek Rysz, Andrzej Rydzewski, Marian Klinger, Rafal Wnuk, Piotr Kozminski, Anna Nocon, Kazimierz Ciechanowski, Pedro Correia, Fernando Neves, José Barata, Gabriel Mircescu, Mihai Voiculescu, Gheorghe Gluhovschi, Eugen Mota, Angel Luís Martín De Francisco, Alberto Torre, Alba Herreros, José Luño, E Gruss, Judith Martins, Marti Vallés, Julio Pascual, Peter Bárány, Andreas H Bock, Patrice M Ambuehl, Sehsuvar Erturk, Mustafa Arici, Saime Paydas, Zeki Soypacaci, Taner Camsari, Sedat Ustundag, Iain C Macdougall, Mark E Thomas, Richard J D'Souza, Jo E Taylor, Nicholas R Pritchard, Robin Jeffery, Stephen G Riley, Deepak Bhatnagar, Sunil Bhandari, David Reaich, Paul E Stevens, Mohsen El Kossi, Simon Roe, Brian Camilleri, Aimun Ahmed, Arif Khwaja, Barbara Thompson, Debasish Banerjee, Johann Nicholas, Alastair Hutchison, Richard Borrows

Abstract

Background: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration.

Methods: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period.

Results: The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups.

Conclusions: These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD.

Keywords: anemia; cardiovascular disease; oxidative stress.

© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA.

Figures

FIGURE 1
FIGURE 1
Patient disposition (safety population). FCM, ferric carboxymaltose.

References

    1. Fishbane S, Pollack S, Feldman HI. et al. Iron indices in chronic kidney disease in the National Health and Nutritional Examination Survey 1988–2004. Clin J Am Soc Nephrol 2009; 4: 57–61
    1. Camaschella C, Strati P. Recent advances in iron metabolism and related disorders. Intern Emerg Med 2010; 5: 393–400
    1. Kidney Disease Improving Global Outcomes (KDIGO). Clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl 2012; 4: 279–335
    1. Macdougall IC. Intravenous iron therapy in non-dialysis CKD patients. Nephrol Dial Transplant 2014; 29: 717–720
    1. Geisser P, Burckhardt S. The pharmacokinetics and pharmacodynamics of iron preparations. Pharmaceutics 2011; 3: 12–33
    1. Vaziri ND. Understanding iron: promoting its safe use in patients with chronic kidney failure treated by hemodialysis. Am J Kidney Dis 2013; 61: 992–1000
    1. Parkkinen J, von Bonsdorff L, Peltonen S. et al. Catalytically active iron and bacterial growth in serum of haemodialysis patients after i.v. iron-saccharate administration. Nephrol Dial Transplant 2000; 15: 1827–1834
    1. Rozen-Zvi B, Gafter-Gvili A, Paul M. et al. Intravenous versus oral iron supplementation for the treatment of anemia in CKD: systematic review and meta-analysis. Am J Kidney Dis 2008; 52: 897–906
    1. Macdougall IC, Bircher AJ, Eckardt KU. et al. Iron management in chronic kidney disease: conclusions from a ‘Kidney Disease: Improving Global Outcomes’ (KDIGO) controversies conference. Kidney Int 2016; 89: 23–39
    1. Macdougall IC, Bock AH, Carrera F. et al. FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in psatient with chronic kidney disease and iron deficiency anaemia. Nephrol Dial Transplant 2014; 29: 2075–2084
    1. Levey AS, Bosch JP, Lewis JB. et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 1999; 130: 461–470
    1. Agarwal R, Kusek JW, Pappas MK. A randomized trial of intravenous and oral iron in chronic kidney disease. Kidney Int 2015; 88: 905–914
    1. Qunibi WY, Martinez C, Smith M. et al. A randomized controlled trial comparing intravenous ferric carboxymaltose with oral iron for treatment of iron deficiency anaemia of non-dialysis-dependent chronic kidney disease patients. Nephrol Dial Transplant 2011; 26: 1599–1607
    1. Kalra PA, Bhandari S, Saxena S. et al. A randomized trial of iron isomaltoside 1000 versus oral iron in non-dialysis-dependent chronic kidney diseasepatients with anaemia. Nephrol Dial Translant 2015; 30: 1577–1589
    1. Moore RA, Gaskell H, Rose P. et al. Meta-analysis of efficacy and safety of intravenous ferric carboxymaltose (Ferinject) from clinical trial reports and published trial data. BMC Blood Disorders 2011; 11: 4.

Source: PubMed

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