Discussion
This invesigator-initiated, multicentre Australian and New Zealand study has been designed to provide evidence to help nephrologists and their CKD patients better determine whether Oxpentifylline (Trental®) administration will safely and effectively treat erythropoietin- or darbepoietin-resistant anaemia. Given that numerous studies have demonstrated that ESA hyporesponsive patients are at significantly increased risk of mortality,[28] novel treatments for correcting anaemia in this group (such as with oxpentifylline) may represent an important strategy for improving clinical outcomes. The multicentre nature of the trial will greatly enhance its generalisability. Moreover, the trial sample size has been carefully and prospectively calculated using a minimum clinically important difference in haemoglobin level of 10 g/L and realistic estimates of trial drop-out and non-compliance rates to minimise the risk of a type 2 statistical error. Demonstration of a significant improvement in haemoglobin levels with oxpentifylline therapy will provide clinicians with an important new strategy for effectively treating ESA-resistant anaemia. On the other hand, a negative study will dissuade clinicians from unnecessarily exposing patients to oxpentifylline (which has a small potential for side effects) if it is proven to lack efficacy with respect to treating ESA-resistant anaemia.
The authors gratefully acknowledge the contributions of all members of the HERO Trial Study Group, dialysis nursing staff, trial co-ordinators, research staff and patients. The invaluable assistance provided by Ms Alicia Smith, Ms Melissa Gardiner and Ms Peta-Anne Paul-Brent from the Australasian Kidney Trials Network is very much appreciated.
The study is funded by grants from the Roche Foundation for Anaemia Research (RoFAR), Amgen and Janssen-Cilag. The funding bodies played no role in the study design; collection, analysis and interpretation of data; writing of the manuscript; or the decision to submit the manuscript for publication.
The study is funded by grants from the Roche Foundation for Anaemia Research (RoFAR), Amgen Australia and Janssen-Cilag.
AKTN = Australasian Kidney Trials Network; CKD = Chronic kidney disease; CRP = C-reactive protein; CTN = Clinical trials notification; DPO = Darbepoetin; EPO = Erythropoietin; ESA = Erythropoiesis stimulating agent; ESKD = End-stage kidney disease; FPN = Ferroportin; HERO = hemoglobin elevation in erythropoietin resistance with oxpentifylline; IFN-γ = Interferon-gamma; IL-1 = Interleukin-1; IL-6 = Interleukin-6; IVRS = Interactive voice response system; MedDRA = Medical dictionary for regulatory activities; SOC = System organ class; TGA = Therapeutic Goods Administration; TNF-α = Tumour necrosis factor alpha.
Corresponding author:* Email, David Wayne Johnson* - david_johnson@health.qld.gov.au ; Carmel Mary Hawley - carmel_hawley@health.qld.gov.au ; Brenda Rosser - Brenda.Rosser@qimr.edu.au ; Elaine Beller - e.beller@uq.edu.au ; Charles Thompson - c.thompson3@uq.edu.au ; Robert G Fassett - Rob.Fassett@dhhs.tas.gov.au ; Paolo Ferrari - paolo.ferrari@health.wa.gov.au ; Stephen MacDonald - stephenm@anzdata.org.au ; Eugenie Pedagogos - eugenie.pedagogos@mh.org.au ; Alan Cass - acass@george.org.au
BMC Nephrology © 2008 Johnson et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Professor Johnson has received consultancy fees and speaker's honoraria from Sanofi-Aventis (manufacturer of oxpentifylline). He has also received consultancy fees, speaker's honoraria, research grants and conference travel sponsorships from Amgen, Janssen-Cilag and Roche (all manufacturers of erythropoiesis stimulating agents).
Dr. Hawley has received conference travel sponsorships from Amgen and Janssen- Cilag.
Professor Ferrari has received speaker's honoraria and conference travel sponsorships from Amgen, Roche and Janssen-Cilag.
Dr McDonald has received speaker's honoraria, and conference travel sponsorships from Amgen and Janssen-Cilag (manufacturers of erythropoiesis stimulating agents).
Associate Professor Alan Cass has received speaker's honoraria and research grants from Amgen, Janssen-Cilag and Roche.
The remaining authors declare that they have no financial competing interests.
Non-Financial Competing Interests
The authors declare that they have no non-financial competing interests.
Authors' Contributions
DJ: Principal Investigator; conceived study; participated in design and co-ordination; helped to draft manuscript; read and approved the final manuscript. CH: Trial Management Committee member; participated in design and co-ordination; helped to draft manuscript; read and approved the final manuscript. BR: Trial Management Committee member; participated in design and co-ordination; helped to draft manuscript; read and approved the final manuscript. EB: Trial Management Committee member; participated in design and co-ordination; provided statistical advice; helped to draft manuscript; read and approved the final manuscript. CT: Trial Management Committee member; participated in design and co-ordination; provided statistical advice; helped to draft manuscript; read and approved the final manuscript. RB: Trial Management Committee member; participated in design and co-ordination; helped to draft manuscript; read and approved the final manuscript. PF: Trial Management Committee member; conceived hepcidin sub-study; participated in design and co-ordination; helped to draft manuscript; read and approved the final manuscript. SM: Trial Management Committee member; participated in design and co-ordination; helped to draft manuscript; read and approved the final manuscript. EP: Trial Management Committee member; participated in design and co-ordination; helped to draft manuscript; read and approved the final manuscript. AC: Trial Management Committee member; participated in design and co-ordination; helped to draft manuscript; read and approved the final manuscript.
Cite this: Oxpentifylline Versus Placebo in the Treatment of Erythropoietin-resistant Anaemia: A Randomized Controlled Trial - Medscape - Aug 01, 2008.
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