Background and aim

Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor

In patients with chronic kidney disease who are not undergoing dialysis, the efficacy and safety of daprodustat compared with conventional eryhtopoiesis-stimulating agent are not known

Methods

Randomized, open-label, phase 3 trial with blinded adjudication of cardiovascular outcomes

Daprodustat was compared with darbepoetin alfa for the treatment of anemia in patients with CKD who were not undergoing dialysis

Primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 and the first occurence of a major adverse cardiovascular event

Results

The mean (±SE) change in the Hb level from baseline to weeks 28 through 52 was 0.74±0.02 g/dL in the daprodustat group and 0.66±0.02 g/dL in the darbepoetin alfa group

During the median follow up of 1.9 years, a first MACE occured in 378 of 1937 patients (19.5%) in the daprodustat group and in 371 of 1935 patients (19.2%) in the darbepoetin alfa group)

The result met the prespecified noninferiority margin of 1.25. The percentages of patients with adverse events were similar in the two groups

Conclusion

In patients with CKD and anemia, not on dialysis, daprodustat was non inferior to darbepoetin alfa with regard to the change in the hemoglobin level from baseline and with respect to cardiovascular outcomes.

Reference: Singh AK, Carroll K, McMurray JJV, et al. Daprodustat for the treatment of anaemia in patients not undergoing dialysis. N Engl J Med. 2021; 385:2313-2324.