A randomised, cross-over study comparing injection site pain with subcutaneous epoetin beta and subcutaneous darbepoetin alfa in patients with chronic kidney disease^*

ABSTRACT

Objective: To compare injection site pain of subcutaneous (sc) epoetin beta and darbepoetin alfa in adult patients with chronic kidney disease.

Research design and methods: This was a multi-centre, randomised, two-arm, single-blind, cross-over study. Patients were randomised to receive weekly sc darbepoetin alfa 30 μg or weekly sc epoetin beta 6000 IU for 2 weeks and were then crossed over to the alternative treatment for 2 weeks. Injection site pain was assessed using a 10 cm ungraduated visual analogue scale (0 = no pain, 10 = worst pain) and a six-point verbal rating scale. Patient preference for treatment was also assessed.

Trial registration: http://clinicaltrials.gov/(NCT00377481).

Results: All randomised patients (N = 48) completed the study. The sample comprised 29 chronic kidney disease patients (Stage 3 or Stage 4), 11 peritoneal dialysis patients and 8 renal transplant patients. Patients perceived significantly less pain with epoetin beta than darbepoetin alfa, using the visual analogue scale (relative pain score = 2.75, darbepoetin alfa:epoetin beta, 95% CI: 1.85, 4.07; p < 0.0001) and the verbal rating scale (median: 0.5, 95% CI: 0.5, 1.0 vs. median: 1.5, 95% CI: 1.0, 2.0; p < 0.0001). Epoetin beta was preferred by significantly more patients (65%) than darbepoetin alfa (10%) (p < 0.001); 25% of patients reported no preference.

Conclusions: Limitations included lack of an epoetin alfa comparator and limited blinding (patients were blinded to treatment, however, an unblinded nurse administered treatment). We show that sc injection of epoetin beta is significantly less painful than darbepoetin alfa and patient preference for epoetin beta confirms that the difference is clinically meaningful.

Key words: :

• Darbepoetin alfa
• Epoetin beta
• Pain
• Subcutaneous injections

Acknowledgements

Declaration of interest: This study was sponsored by Roche Products Pty Limited. S.D.R. has received grant/research support, travel grants and honoraria from Amgen and Roche, and has been an advisory board member for both companies. M.G.S. has received research support and travel/educational grants from Amgen, Roche and Janssen-Cilag, and is currently an advisory board member for Roche. R.G.W. has received research support, travel/educational grants and honoraria from Amgen, Roche and Janssen-Cilag, and has been an advisory board member for all three companies. Peter Tobin (Roche) provided assistance in the preparation of this article. Independent medical writing assistance was provided by ProScribe Medical Communications and this was funded by an unrestricted financial grant from Roche Products Pty Limited.

COMFORT study group: Alex Disney, Queen Elizabeth Hospital, Adelaide; Nicole M. Isbel, Princess Alexandra Hospital, Brisbane; Lukas Kairaitis, Westmead Hospital, Sydney; Carol A. Pollock, Royal North Shore Hospital, Sydney; Fiona G. Brown, Monash Medical Centre, Melbourne; Josephine Chow, Liverpool Hospital, Sydney; Matt I. Truman and Kellie A. Ulyate, Roche Products Pty Limited, Sydney. All of the above-mentioned study group members met the ICMJE criteria for authorship and are to be considered as co-authors on this article.

The authors acknowledge the contribution of the key study co-ordinators: Elizabeth Bohringer, Bronwyn Hockley, Jenny Edmunds, Tania Smolonogov, Holly Anderson, Jacqueline Pearse and Jyotsna Nandkumar. The authors also acknowledge the contribution of the other study coordinators, pharmacists and co-investigators at each site.

Notes

* Findings previously presented at the American Society of Nephrology Renal Week, 31 October–5 November 2007, San Francisco, CA, USA