Maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly: a randomized comparative trial

Fernando Carrera, Charmaine E Lok, Angel de Francisco, Francesco Locatelli, Johannes F E Mann, Bernard Canaud, Peter G Kerr, Iain C Macdougall, Anatole Besarab, Giuseppe Villa, Isabelle Kazes, Bruno Van Vlem, Shivinder Jolly, Ulrich Beyer, Frank C Dougherty, PATRONUS Investigators, Pierre Bataille, Jean Louis Bouchet, Bernard Canaud, François Combarnous, Hafed Fessi, Christine Fumeron, Atman Haddj Elmrabet, Isabelle Kazes, Maurice Laville, Alain Lyon, Fabien Metivier, Catherine Michel Aura, Philippe Rieu, Jean Pierre Rivory, Jean Philippe Ryckelynck, Kim Seng Ang, Henri Hemile Thebaud, Philippe Zaoui, Alberto Albertazzi, Marcello Amato, Giuseppe Cannella, Giuseppe Bonforte, Francesco Locatelli, Pietro Marchini, Antonio Santoro, Giuseppe Villa, José Maria Alcazar, Pedro Aljama, Javier Arrieta, Francisco Barbosa Puig, Alberto Barrientos, Jordi Bonall Bastons, Luis Gonzalez, Manuel Granda, Francesc Maduell Canals, Angel Luis Martin de Francisco, Jesus Olivares Martin, Alfonso Otero, Damaso Sanz Guajardo, Rafaels Selgas, Serge Cournoyer, Shivinder Jolly, Charmaine Lok, Jennifer Macrae, Chris Rabbat, Richard Turcot, Gordon Wong, Deborah Zimmerman, Johannes Mann, Thomas Schneider, Peter Thon, Guenter Vollgraf, Thomas Weinreich, Rainer Woitas, Max Dratwa, Eric Goffin, Bart Maes, Bruno Van Vlem, Alastair Hutchison, Iain Macdougall, Robert Mactier, A Peter Maxwell, Paul Stevens, Fernando Carrera, Randall Faull, David Johnson, Peter Kerr, Simon Roger, Rowan Walker, Walter Hörl, Renate Klauser-Braun, Rainer Oberbauer, Andreas Hans Bock, Kaj Metsarinne, Heikki Saha, Jeppe Hagstrup, Ove Oestergaard, Fernando Carrera, Charmaine E Lok, Angel de Francisco, Francesco Locatelli, Johannes F E Mann, Bernard Canaud, Peter G Kerr, Iain C Macdougall, Anatole Besarab, Giuseppe Villa, Isabelle Kazes, Bruno Van Vlem, Shivinder Jolly, Ulrich Beyer, Frank C Dougherty, PATRONUS Investigators, Pierre Bataille, Jean Louis Bouchet, Bernard Canaud, François Combarnous, Hafed Fessi, Christine Fumeron, Atman Haddj Elmrabet, Isabelle Kazes, Maurice Laville, Alain Lyon, Fabien Metivier, Catherine Michel Aura, Philippe Rieu, Jean Pierre Rivory, Jean Philippe Ryckelynck, Kim Seng Ang, Henri Hemile Thebaud, Philippe Zaoui, Alberto Albertazzi, Marcello Amato, Giuseppe Cannella, Giuseppe Bonforte, Francesco Locatelli, Pietro Marchini, Antonio Santoro, Giuseppe Villa, José Maria Alcazar, Pedro Aljama, Javier Arrieta, Francisco Barbosa Puig, Alberto Barrientos, Jordi Bonall Bastons, Luis Gonzalez, Manuel Granda, Francesc Maduell Canals, Angel Luis Martin de Francisco, Jesus Olivares Martin, Alfonso Otero, Damaso Sanz Guajardo, Rafaels Selgas, Serge Cournoyer, Shivinder Jolly, Charmaine Lok, Jennifer Macrae, Chris Rabbat, Richard Turcot, Gordon Wong, Deborah Zimmerman, Johannes Mann, Thomas Schneider, Peter Thon, Guenter Vollgraf, Thomas Weinreich, Rainer Woitas, Max Dratwa, Eric Goffin, Bart Maes, Bruno Van Vlem, Alastair Hutchison, Iain Macdougall, Robert Mactier, A Peter Maxwell, Paul Stevens, Fernando Carrera, Randall Faull, David Johnson, Peter Kerr, Simon Roger, Rowan Walker, Walter Hörl, Renate Klauser-Braun, Rainer Oberbauer, Andreas Hans Bock, Kaj Metsarinne, Heikki Saha, Jeppe Hagstrup, Ove Oestergaard

Abstract

Background: Several studies with erythropoiesis-stimulating agents claim that maintenance therapy of renal anaemia may be possible at extended dosing intervals; however, few studies were randomized, results varied, and comparisons between agents were absent. We report results of a multi-national, randomized, prospective trial comparing haemoglobin maintenance with methoxy polyethylene glycol-epoetin beta and darbepoetin alfa administered once monthly.

Methods: Haemodialysis patients (n = 490) on stable once-weekly intravenous darbepoetin alfa were randomized to methoxy polyethylene glycol-epoetin beta once monthly or darbepoetin alfa every 2 weeks for 26 weeks, with dose adjustment for individual haemoglobin target (11-13 g/dL; maximum decrease from baseline 1 g/dL). Subsequently, patients entered a second 26-week period of once-monthly methoxy polyethylene glycol-epoetin beta and darbepoetin alfa. The primary endpoint was the proportion of patients who maintained average haemoglobin ≥10.5 g/dL, with a decrease from baseline ≤1 g/dL, in Weeks 50-53; the secondary endpoint was dose change over time. The trial is registered at www.ClinicalTrials.gov, number NCT00394953.

Results: Baseline characteristics were similar between groups. One hundred and fifty-seven of 245 patients treated with methoxy polyethylene glycol-epoetin beta and 99 of 245 patients with darbepoetin alfa met the response definition (64.1% and 40.4%; P < 0.0001). Doses increased by 6.8% with methoxy polyethylene glycol-epoetin beta and 58.8% with darbepoetin alfa during once-monthly treatment. Death rates were equal between treatments (5.7%). Most common adverse events included hypertension, procedural hypotension, nasopharyngitis and muscle spasms, with no differences between groups.

Conclusions: Methoxy polyethylene glycol-epoetin beta maintained target haemoglobin more successfully than darbepoetin alfa at once-monthly dosing intervals despite dose increases with darbepoetin alfa.

Figures

Fig. 1
Fig. 1
Screening and enrolment of study patients.
Fig. 2
Fig. 2
Treatment protocol. R = randomization.
Fig. 3
Fig. 3
Median haemoglobin values over time with interquartile range (intent-to-treat population).

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