Cargando…

The Ferumoxytol for Anemia of CKD Trial (FACT)—a randomized controlled trial of repeated doses of ferumoxytol or iron sucrose in patients on hemodialysis: background and rationale

BACKGROUND: Iron deficiency anemia (IDA) is a common manifestation of chronic kidney disease (CKD), affecting most patients on hemodialysis and imposing a substantial clinical burden. Treatment with iron supplementation increases hemoglobin levels and can reduce the severity of anemia in patients wi...

Descripción completa

Detalles Bibliográficos
Autores principales: Macdougall, Iain C., Dahl, Naomi V., Bernard, Kristine, Li, Zhu, Batyky, Alka, Strauss, William E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379516/
https://www.ncbi.nlm.nih.gov/pubmed/28372549
http://dx.doi.org/10.1186/s12882-017-0523-8
_version_ 1782519622106349568
author Macdougall, Iain C.
Dahl, Naomi V.
Bernard, Kristine
Li, Zhu
Batyky, Alka
Strauss, William E.
author_facet Macdougall, Iain C.
Dahl, Naomi V.
Bernard, Kristine
Li, Zhu
Batyky, Alka
Strauss, William E.
author_sort Macdougall, Iain C.
collection PubMed
description BACKGROUND: Iron deficiency anemia (IDA) is a common manifestation of chronic kidney disease (CKD), affecting most patients on hemodialysis and imposing a substantial clinical burden. Treatment with iron supplementation increases hemoglobin levels and can reduce the severity of anemia in patients with CKD. While correcting anemia in these patients is an important therapeutic goal, there is a lack of long-term trials directly comparing intravenous iron therapies in patients with CKD receiving hemodialysis. METHODS/DESIGN: The Ferumoxytol for Anemia of CKD Trial (FACT) is a 13-month, open-label, randomized, multicenter, international, prospective study with 2 substudies. Entry criteria for the main study include adults with IDA (defined as hemoglobin <11.5 g/dL [<115.0 g/L] and a transferrin saturation <30%), serum ferritin <800 ng/mL (<1798 pmol/L), and receiving hemodialysis for ≥3 months. Patients are randomized to receive ferumoxytol (1.02 g over 2 doses) or iron sucrose (1.0 g over 10 doses) during the initial 5-week treatment period. Those with persistent/recurrent IDA over the 11-month observation period will receive additional 5-week treatment periods, as appropriate. The primary efficacy endpoint of the main study is the mean change in hemoglobin from Baseline to Week 5 for each treatment period. The secondary efficacy endpoints include the mean change in transferrin saturation from Baseline to Week 5 and the proportion of patients with a hemoglobin increase of ≥1.0 g/dL at any time from Baseline to Week 5. Safety will be assessed through an examination of the adverse event profile over the course of the study. An “oxidative stress” substudy in approximately 100 patients will assess the effects of treatment on biomarkers of oxidative stress/inflammation during the initial 5-week treatment period, and a magnetic resonance imaging substudy in approximately 70 patients will assess the potential for iron deposition in target tissues over 24 months. DISCUSSION: FACT fulfills the need for a long-term comparative trial in patients with IDA and CKD receiving hemodialysis. The efficacy and safety results will provide useful information for guiding therapy in this population. Two hundred ninety-six patients have been enrolled, and completion of the main study is expected soon. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01227616 (registered October 22, 2010); EudraCT number: 2010-022133-28
format Online
Article
Text
id pubmed-5379516
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-53795162017-04-07 The Ferumoxytol for Anemia of CKD Trial (FACT)—a randomized controlled trial of repeated doses of ferumoxytol or iron sucrose in patients on hemodialysis: background and rationale Macdougall, Iain C. Dahl, Naomi V. Bernard, Kristine Li, Zhu Batyky, Alka Strauss, William E. BMC Nephrol Study Protocol BACKGROUND: Iron deficiency anemia (IDA) is a common manifestation of chronic kidney disease (CKD), affecting most patients on hemodialysis and imposing a substantial clinical burden. Treatment with iron supplementation increases hemoglobin levels and can reduce the severity of anemia in patients with CKD. While correcting anemia in these patients is an important therapeutic goal, there is a lack of long-term trials directly comparing intravenous iron therapies in patients with CKD receiving hemodialysis. METHODS/DESIGN: The Ferumoxytol for Anemia of CKD Trial (FACT) is a 13-month, open-label, randomized, multicenter, international, prospective study with 2 substudies. Entry criteria for the main study include adults with IDA (defined as hemoglobin <11.5 g/dL [<115.0 g/L] and a transferrin saturation <30%), serum ferritin <800 ng/mL (<1798 pmol/L), and receiving hemodialysis for ≥3 months. Patients are randomized to receive ferumoxytol (1.02 g over 2 doses) or iron sucrose (1.0 g over 10 doses) during the initial 5-week treatment period. Those with persistent/recurrent IDA over the 11-month observation period will receive additional 5-week treatment periods, as appropriate. The primary efficacy endpoint of the main study is the mean change in hemoglobin from Baseline to Week 5 for each treatment period. The secondary efficacy endpoints include the mean change in transferrin saturation from Baseline to Week 5 and the proportion of patients with a hemoglobin increase of ≥1.0 g/dL at any time from Baseline to Week 5. Safety will be assessed through an examination of the adverse event profile over the course of the study. An “oxidative stress” substudy in approximately 100 patients will assess the effects of treatment on biomarkers of oxidative stress/inflammation during the initial 5-week treatment period, and a magnetic resonance imaging substudy in approximately 70 patients will assess the potential for iron deposition in target tissues over 24 months. DISCUSSION: FACT fulfills the need for a long-term comparative trial in patients with IDA and CKD receiving hemodialysis. The efficacy and safety results will provide useful information for guiding therapy in this population. Two hundred ninety-six patients have been enrolled, and completion of the main study is expected soon. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01227616 (registered October 22, 2010); EudraCT number: 2010-022133-28 BioMed Central 2017-04-03 /pmc/articles/PMC5379516/ /pubmed/28372549 http://dx.doi.org/10.1186/s12882-017-0523-8 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Study Protocol
Macdougall, Iain C.
Dahl, Naomi V.
Bernard, Kristine
Li, Zhu
Batyky, Alka
Strauss, William E.
The Ferumoxytol for Anemia of CKD Trial (FACT)—a randomized controlled trial of repeated doses of ferumoxytol or iron sucrose in patients on hemodialysis: background and rationale
title The Ferumoxytol for Anemia of CKD Trial (FACT)—a randomized controlled trial of repeated doses of ferumoxytol or iron sucrose in patients on hemodialysis: background and rationale
title_full The Ferumoxytol for Anemia of CKD Trial (FACT)—a randomized controlled trial of repeated doses of ferumoxytol or iron sucrose in patients on hemodialysis: background and rationale
title_fullStr The Ferumoxytol for Anemia of CKD Trial (FACT)—a randomized controlled trial of repeated doses of ferumoxytol or iron sucrose in patients on hemodialysis: background and rationale
title_full_unstemmed The Ferumoxytol for Anemia of CKD Trial (FACT)—a randomized controlled trial of repeated doses of ferumoxytol or iron sucrose in patients on hemodialysis: background and rationale
title_short The Ferumoxytol for Anemia of CKD Trial (FACT)—a randomized controlled trial of repeated doses of ferumoxytol or iron sucrose in patients on hemodialysis: background and rationale
title_sort ferumoxytol for anemia of ckd trial (fact)—a randomized controlled trial of repeated doses of ferumoxytol or iron sucrose in patients on hemodialysis: background and rationale
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379516/
https://www.ncbi.nlm.nih.gov/pubmed/28372549
http://dx.doi.org/10.1186/s12882-017-0523-8
work_keys_str_mv AT macdougalliainc theferumoxytolforanemiaofckdtrialfactarandomizedcontrolledtrialofrepeateddosesofferumoxytolorironsucroseinpatientsonhemodialysisbackgroundandrationale
AT dahlnaomiv theferumoxytolforanemiaofckdtrialfactarandomizedcontrolledtrialofrepeateddosesofferumoxytolorironsucroseinpatientsonhemodialysisbackgroundandrationale
AT bernardkristine theferumoxytolforanemiaofckdtrialfactarandomizedcontrolledtrialofrepeateddosesofferumoxytolorironsucroseinpatientsonhemodialysisbackgroundandrationale
AT lizhu theferumoxytolforanemiaofckdtrialfactarandomizedcontrolledtrialofrepeateddosesofferumoxytolorironsucroseinpatientsonhemodialysisbackgroundandrationale
AT batykyalka theferumoxytolforanemiaofckdtrialfactarandomizedcontrolledtrialofrepeateddosesofferumoxytolorironsucroseinpatientsonhemodialysisbackgroundandrationale
AT strausswilliame theferumoxytolforanemiaofckdtrialfactarandomizedcontrolledtrialofrepeateddosesofferumoxytolorironsucroseinpatientsonhemodialysisbackgroundandrationale
AT macdougalliainc ferumoxytolforanemiaofckdtrialfactarandomizedcontrolledtrialofrepeateddosesofferumoxytolorironsucroseinpatientsonhemodialysisbackgroundandrationale
AT dahlnaomiv ferumoxytolforanemiaofckdtrialfactarandomizedcontrolledtrialofrepeateddosesofferumoxytolorironsucroseinpatientsonhemodialysisbackgroundandrationale
AT bernardkristine ferumoxytolforanemiaofckdtrialfactarandomizedcontrolledtrialofrepeateddosesofferumoxytolorironsucroseinpatientsonhemodialysisbackgroundandrationale
AT lizhu ferumoxytolforanemiaofckdtrialfactarandomizedcontrolledtrialofrepeateddosesofferumoxytolorironsucroseinpatientsonhemodialysisbackgroundandrationale
AT batykyalka ferumoxytolforanemiaofckdtrialfactarandomizedcontrolledtrialofrepeateddosesofferumoxytolorironsucroseinpatientsonhemodialysisbackgroundandrationale
AT strausswilliame ferumoxytolforanemiaofckdtrialfactarandomizedcontrolledtrialofrepeateddosesofferumoxytolorironsucroseinpatientsonhemodialysisbackgroundandrationale