The CREATE trial - building the evidence

Renal anaemia is an independent risk factor for the development of left ventricular hypertrophy (LVH), heart failure and mortality. Studies show that partial correction of anaemia leads to partial regression of LVH. However, early initiation of anaemia therapy may be the optimal way to reduce cardiac morbidity and mortality. The Cardiovascular risk Reduction by Early Anemia Treatment with Epoetin Beta (CREATE) trial will investigate the effect of early anaemia correction on cardiovascular risk reduction in patients not yet on renal replacement therapy. The primary objectives of this open, randomized, multicentre trial are to investigate the effect of early anaemia correction on the change in left ventricular mass index after 1 year, and the time to first cardiovascular event. The trial comprises two treatment arms: early intervention where patients will receive epoetin beta when their haemoglobin (Hb) level is 11-12.5 g/dl and their target Hb will be 13-15 g/dl, and late intervention, where patients will receive epoetin beta once their Hb level is < 10.5 g/dl and their target Hb will be 10.5-11.5 g/dl. The study will be event-driven with a continuous evaluation and an interim analysis once every year. The inclusion of 600 patients is based on assumption of a 15-20% event rate in the control group and that 200 events are needed to detect a reduction of about one-third. In conclusion, the CREATE trial will examine whether early anaemia treatment will prevent development of LVH, reduce cardiovascular morbidity and provide other benefits.