Safety and efficacy of iron isomaltoside 1000/ferric derisomaltose versus iron sucrose in patients with chronic kidney disease: the FERWON-NEPHRO randomized, open-label, comparative trial

被引:62
作者
Bhandari, Sunil [1 ]
Kalra, Philip A. [2 ]
Berkowitz, Mario [3 ]
Belo, Diogo [4 ]
Thomsen, Lars L. [5 ]
Wolf, Myles [6 ]
机构
[1] Hull Univ Teaching Hosp NHS Trust, Dept Renal Med, Kingston Upon Hull, Yorks, England
[2] Salford Royal NHS Fdn Trust, Dept Renal Med, Salford, Lancs, England
[3] Leon Med Res, Miami, FL USA
[4] Calif Inst Renal Res, Chula Vista, CA USA
[5] Pharmacosmos AS, Dept Clin & Nonclin Res, Holbaek, Denmark
[6] Duke Univ, Sch Med, Dept Med, Div Nephrol,Duke Clin Res Inst, Durham, NC 27706 USA
关键词
ferric derisomaltose; iron deficiency anaemia; iron isomaltoside 1000; iron treatment; HEART-FAILURE; ORAL IRON; FERRIC CARBOXYMALTOSE; 1000 MONOFER(R); ANEMIA; INFUSION; THERAPY; DISCREPANCY;
D O I
10.1093/ndt/gfaa011
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Background. The optimal intravenous (IV) iron would allow safe correction of iron deficiency at a single infusion over a short time. The FERWON-NEPHRO trial evaluated the safety and efficacy of iron isomaltoside 1000/ferric derisomaltose (IIM) in patients with non-dialysis-dependent chronic kidney disease and iron deficiency anaemia. Methods. In this randomized, open-label and multi-centre trial conducted in the USA, patients were randomized 2:1 to a single dose of 1000 mg IIM or iron sucrose (IS) administered as 200 mg IV injections up to five times within a 2-week period. The co-primary endpoints were serious or severe hypersensitivity reactions and change in haemoglobin (Hb) from baseline to Week 8. Secondary endpoints included incidence of composite cardiovascular adverse events (AEs). Results. A total of 1538 patients were enrolled (mean estimated glomerular filtration rate 35.5mL/min/1.73m(2)). The co-primary safety objective was met based on no significant difference in the incidence of serious or severe hypersensitivity reactions in the IIM and IS groups [0.3% versus 0%; risk difference: 0.29% (95% confidence interval: -0.19; 0.77; P>0.05)]. Incidence of composite cardiovascular AEs was significantly lower in the IIM versus IS group (4.1% versus 6.9%; P=0.025). Compared with IS, IIM led to a more pronounced increase in Hb during the first 4 weeks (P <= 0.021), and change in Hb to Week 8 showed non-inferiority, confirming that the co-primary efficacy objective was met. Conclusions. Compared with multiple doses of IS, a single dose of IIM induced a non-inferior 8-week haematological response, comparably low rates of hypersensitivity reactions, and a significantly lower incidence of composite cardiovascular AEs.
引用
收藏
页码:111 / 120
页数:10
相关论文
共 34 条
[1]   New data on the safety of IV iron-but why the discrepancy with FIND-CKD? Reply [J].
Agarwal, Rajiv .
KIDNEY INTERNATIONAL, 2015, 88 (06) :1446-1447
[2]   A randomized trial of intravenous and oral iron in chronic kidney disease [J].
Agarwal, Rajiv ;
Kusek, John W. ;
Pappas, Maria K. .
KIDNEY INTERNATIONAL, 2015, 88 (04) :905-914
[3]   Ferric Carboxymaltose in Patients with Heart Failure and Iron Deficiency. [J].
Anker, Stefan D. ;
Comin Colet, Josep ;
Filippatos, Gerasimos ;
Willenheimer, Ronnie ;
Dickstein, Kenneth ;
Drexler, Helmut ;
Luescher, Thomas F. ;
Bart, Boris ;
Banasiak, Waldemar ;
Niegowska, Joanna ;
Kirwan, Bridget-Anne ;
Mori, Claudio ;
Rothe, Barbara von Eisenhart ;
Pocock, Stuart J. ;
Poole-Wilson, Philip A. ;
Ponikowski, Piotr .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (25) :2436-2448
[4]  
[Anonymous], 2012, Kidney International Supplements
[5]   Data confusion [J].
Bhandari, Sunil ;
Kalra, Philip A. ;
Coyne, Daniel W. .
KIDNEY INTERNATIONAL, 2015, 88 (06) :1445-1445
[6]   A randomized, open-label trial of iron isomaltoside 1000 (MonoferA®) compared with iron sucrose (VenoferA®) as maintenance therapy in haemodialysis patients [J].
Bhandari, Sunil ;
Kalra, Philip A. ;
Kothari, Jatin ;
Ambuehl, Patrice M. ;
Christensen, Jeppe H. ;
Essaian, Ashot M. ;
Thomsen, Lars L. ;
Macdougall, Iain C. ;
Coyne, Daniel W. .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2015, 30 (09) :1577-1589
[7]   A Randomized Noninferiority Trial of Intravenous Iron Isomaltoside versus Oral Iron Sulfate in Patients with Nonmyeloid Malignancies and Anemia Receiving Chemotherapy: The PROFOUND Trial [J].
Birgegard, Gunnar ;
Henry, David ;
Glaspy, John ;
Chopra, Rakesh ;
Thomsen, Lars L. ;
Auerbach, Michael .
PHARMACOTHERAPY, 2016, 36 (04) :402-414
[8]   Effect of Iron Isomaltoside on Skeletal Muscle Energetics in Patients With Chronic Heart Failure and Iron Deficiency: FERRIC-HF II Randomized Mechanistic Trial [J].
Charles-Edwards, Geoffrey ;
Amaral, Nelson ;
Sleigh, Alison ;
Ayis, Salma ;
Catibog, Norman ;
McDonagh, Theresa ;
Monaghan, Mark ;
Amin-Youssef, George ;
Kemp, Graham J. ;
Shah, Ajay M. ;
Okonko, Darlington O. .
CIRCULATION, 2019, 139 (21) :2386-2398
[9]   High-dose fast infusion of parenteral iron isomaltoside is efficacious in inflammatory bowel disease patients with iron-deficiency anaemia without profound changes in phosphate or fibroblast growth factor 23 [J].
Dahlerup, Jens Frederik ;
Jacobsen, Bent A. ;
van der Woude, Janneke ;
Bark, Lars-Ake ;
Thomsen, Lars L. ;
Lindgren, Stefan .
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 2016, 51 (11) :1332-1338
[10]   A randomized trial of iron isomaltoside versus iron sucrose in patients with iron deficiency anemia [J].
Derman, Richard ;
Roman, Eloy ;
Modiano, Manuel R. ;
Achebe, Maureen M. ;
Thomsen, Lars L. ;
Auerbach, Michael .
AMERICAN JOURNAL OF HEMATOLOGY, 2017, 92 (03) :286-291