Document Detail


Peginesatide in patients with anemia undergoing hemodialysis.
MedLine Citation:
PMID:  23343061     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Peginesatide, a synthetic peptide-based erythropoiesis-stimulating agent (ESA), is a potential therapy for anemia in patients with advanced chronic kidney disease.
METHODS: We conducted two randomized, controlled, open-label studies (EMERALD 1 and EMERALD 2) involving patients undergoing hemodialysis. Cardiovascular safety was evaluated by analysis of an adjudicated composite safety end point--death from any cause, stroke, myocardial infarction, or serious adverse events of congestive heart failure, unstable angina, or arrhythmia--with the use of pooled data from the two EMERALD studies and two studies involving patients not undergoing dialysis. In the EMERALD studies, 1608 patients received peginesatide once monthly or continued to receive epoetin one to three times a week, with the doses adjusted as necessary to maintain a hemoglobin level between 10.0 and 12.0 g per deciliter for 52 weeks or more. The primary efficacy end point was the mean change from the baseline hemoglobin level to the mean level during the evaluation period; noninferiority was established if the lower limit of the two-sided 95% confidence interval was -1.0 g per deciliter or higher in the comparison of peginesatide with epoetin. The aim of evaluating the composite safety end point in the pooled cohort was to exclude a hazard ratio with peginesatide relative to the comparator ESA of more than 1.3.
RESULTS: In an analysis involving 693 patients from EMERALD 1 and 725 from EMERALD 2, peginesatide was noninferior to epoetin in maintaining hemoglobin levels (mean between-group difference, -0.15 g per deciliter; 95% confidence interval [CI], -0.30 to -0.01 in EMERALD 1; and 0.10 g per deciliter; 95% CI, -0.05 to 0.26 in EMERALD 2). The hazard ratio for the composite safety end point was 1.06 (95% CI, 0.89 to 1.26) with peginesatide relative to the comparator ESA in the four pooled studies (2591 patients) and 0.95 (95% CI, 0.77 to 1.17) in the EMERALD studies. The proportions of patients with adverse and serious adverse events were similar in the treatment groups in the EMERALD studies. The cardiovascular safety of peginesatide was similar to that of the comparator ESA in the pooled cohort.
CONCLUSIONS: Peginesatide, administered monthly, was as effective as epoetin, administered one to three times per week, in maintaining hemoglobin levels in patients undergoing hemodialysis. (Funded by Affymax and Takeda Pharmaceutical; ClinicalTrials.gov numbers, NCT00597753 [EMERALD 1], NCT00597584 [EMERALD 2], NCT00598273 [PEARL 1], and NCT00598442 [PEARL 2].).
Authors:
Steven Fishbane; Brigitte Schiller; Francesco Locatelli; Adrian C Covic; Robert Provenzano; Andrzej Wiecek; Nathan W Levin; Mark Kaplan; Iain C Macdougall; Carol Francisco; Martha R Mayo; Krishna R Polu; Anne-Marie Duliege; Anatole Besarab;
Publication Detail:
Type:  Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The New England journal of medicine     Volume:  368     ISSN:  1533-4406     ISO Abbreviation:  N. Engl. J. Med.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-24     Completed Date:  2013-02-01     Revised Date:  2013-11-01    
Medline Journal Info:
Nlm Unique ID:  0255562     Medline TA:  N Engl J Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  307-19     Citation Subset:  AIM; IM    
Affiliation:
Hofstra North Shore-LIJ School of Medicine, Great Neck, NY 11021, USA. sfishbane@nshs.edu
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00597584;  NCT00597753;  NCT00598273;  NCT00598442
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MeSH Terms
Descriptor/Qualifier:
Aged
Anemia / drug therapy*,  etiology
Antibodies / blood
Disease-Free Survival
Drug Administration Schedule
Erythropoietin / adverse effects,  therapeutic use*
Female
Hematinics / adverse effects,  therapeutic use*
Hemoglobins / analysis
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Peptides / adverse effects,  immunology,  therapeutic use*
Renal Dialysis* / adverse effects
Renal Insufficiency, Chronic / blood,  complications,  mortality,  therapy*
Chemical
Reg. No./Substance:
0/Antibodies; 0/Hematinics; 0/Hemoglobins; 0/Peptides; 0/peginesatide; 11096-26-7/Erythropoietin
Investigator
Investigator/Affiliation:
Brigitte Schiller / ; Brigitte Schiller / ; Roderick Clark / ; Claudia Hura / ; Steven Zeig / ; Steven V Lewinski / ; Thomas Whelan / ; Ajay Gupta / ; Aamir Jamal / ; Christopher J LeBrun / ; Darrell Hirt / ; Lawrence Lehrner / ; Michael Roppolo / ; George Nassar / ; Kamal Gandhi / ; Daniel Coyne / ; M Reza Mizani / ; Steven G Achinger / ; Mohammad Ismail / ; George Fadda / ; Samatha Chandupatla / ; Frederick C Whittier / ; Raja Zabaneh / ; K Adu Ntoso / ; Diogo Belo / ; Dennis L Ross / ; Mohamed El-Shahawy / ; Thomas Wooldridge / ; Mario Henriquez / ; Samia Khwaja / ; William Restrepo / ; Jesus Ramirez / ; Ambrose Y Tsang / ; Leland E Garrett / ; Warren Shapiro / ; Mark R Kaplan / ; A Kaldun Nossuli / ; Theodore Herman / ; Rebecca J Schmidt / ; Mary T McNeer / ; Arnold H Kim / ; James R Cotton / ; Paul W Crawford / ; Purushottam Reddy / ; Wadi Suki / ; Robert A Gutman / ; Geoffrey A Block / ; Kenneth Liss / ; Nathan Levin / ; David Roer / ; Nelson Kopyt / ; Tsr Murugan / ; Walid N Ghantous / ; Mahmoud El-Khatib / ; Osahon Ukponmwan / ; Steven H Ong / ; Steven R Tolkan / ; Jared Sugihara / ; Naheed Ansari / ; Anjay Rastogi / ; Allen R Nissenson / ; Zeev Sharon / ; Ahmed Aqeel / ; Uday Desai / ; Maher Azer / ; Anil Agarwal / ; Christopher Brown / ; Aaron Francis Kulick / ; Andrew C Bland / ; David W Koeper / ; Pusadee Lilavivathana Suchinda / ; Renuka Sothinathan / ; Izuchukwu E Nwakoby / ; Baudouin Leclercq / ; Thomas A Krahn / ; Laura Mulloy / ; Joachim Hertel / ; Atif A Qureshi / ; Francisco Zornosa / ; Geethanjali Ramamurthy / ; Howard J Alfred / ; Ramon Mendez / ; Nicholas Hunt / ; Neil Kumar / ; Thomas DelGiorno / ; G Edward Newman / ; Edward D Himot / ; Vijaykumar Rao / ; Istvan Bognar / ; Mario O Belledonne / ; Ramakant Mulay / ; Duane Wombolt / ; Anand N Hiremath / ; Efrain Reisin / ; Saeid Nosrati / ; Clinton Edwards / ; Richard G D'Mello / ; Victor A Klimas / ; Lee E Anderson / ; Lionel Charme Abbott / ; Khalil U Rahman / ; Anatole Besarab / ; Francesco Locatelli / ; Adrian C Covic / ; Edouard Martin / ; Marializa V Bernardo / ; Pablo E Pergola / ; Bhasker R Mehta / ; Chika Oguagha / ; Jieshi Yan / ; Riad Darwish / ; John H Durham / ; Steven Wright / ; Robert Provenzano / ; Anatole Besarab / ; Matthew L Esson / ; Susan V Yue / ; Michael Levine / ; James K Saiki / ; Mohammad Akmal / ; A Kaldun Nossuli / ; Bruce Spinowitz / ; Juan Fernandez / ; Alfred A Jacobs / ; Rasib Raja / ; Kenneth Lempert / ; David J Leehey / ; Rekha Halligan / ; Edgardo L Pellegrini / ; Robert Lynn / ; Chris Sholer / ; Kenneth Cline / ; Paul Dykes / ; Abdul Abukurah / ; Venu Kondle / ; Richard Cottiero / ; Jeffrey Alan Kraut / ; Chao Sun / ; Ali Assefi / ; Robert F McCrary / ; Joseph Aiello / ; Edgardo Laurel / ; Mohammad A Kashif / ; Michael Germain / ; Vasil Todorov / ; Nencho Nenchev / ; Kiril Nenov / ; Radka Karagyozova / ; Zdravko Kraev / ; Blago Blagov / ; Loris Manuelyan / ; Adrian Constantin Covic / ; Stephan Stuht / ; Catalina Luminita Ardelean / ; Lilyana Kambova / ; Petar Shikov / ; Pavlina Paunova / ; Margarita Velkova / ; Wolfgang Backs / ; Andreu Foraster Roselló / ; Dariusz Stryjewski / ; Giuseppe Bonforte / ; Stefan Krivoshiev / ; Wieslaw Klatko / ; Iain Macdougall / ; Thomas Rath / ; Alberto Albertazzi / ; José Portolés / ; Valentin Mushekov / ; Carlos Santiago Guervos / ; Bernard Canaud / ; Gabriel Choukroun / ; Iain MacPhee / ; Marcello Amato / ; Ashraf Ishak Mikhail / ; Mysore Phanish / ; Jonathan Kwan / ; Volker Belwe / ; Francesco Locatelli / ; Fabio Malberti / ; Angel De Francisco / ; Alberto Martinez Castelao / ; Florencio Garcia Martin / ; Jose Alcazar de la Ossa / ; Victorio Menoyo Calonge / ; Dorin Ionescu / ; Muhammad Magdi Yaqoob / ; Janusz Ostrowski / ; Enric Andres Ribes / ; Javier Nieto / ; Piotr Seniuta / ; Andrzej Wiecek / ; Robert Nicholas Foley / ; Jeffery S Berns / ; Brent Alan Blumenstein / ; Ravi I Thadhani / ; Michael H Humphreys / ; Joseph L Blackshear / ; Jonathan G Howlett / ; Frederick A Masoudi / ; Andrew D Michaels / ; Robert E Safford / ; David J Whellan / ; Kyra J Becker / ; Robert Hart / ; Dawn McGuire /
Comments/Corrections
Comment In:
N Engl J Med. 2013 Jan 24;368(4):387-9   [PMID:  23343068 ]
Am J Kidney Dis. 2013 Oct;62(4):659-61   [PMID:  23810692 ]

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