Aims: Hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors have been developed for the treatment of renal anaemia; however, no study has evaluated the safety and efficacy of HIF-PH inhibitors in patients with heart failure (HF). This study was designed to evaluate the safety and efficacy of daprodustat, a HIF-PH inhibitor, in patients with HF and renal anaemia.
Methods and results: We designed a pilot, multi-centre, open-label, randomized controlled study, in which 50 patients with HF complicated with chronic kidney disease and anaemia will be randomized 1:1 to either the daprodustat or control group at seven sites in Japan. Study entry requires New York Heart Association Class II HF symptoms or a history of hospitalization due to HF, an estimated glomerular filtration rate of <60 mL/min/1.73 m2 , and a haemoglobin level of 7.5 to <11.0 g/dl. Patients randomized to the daprodustat group will be treated with oral daprodustat, and the dose will be uptitrated according to the changes in the haemoglobin level from previous visits. In this study, we will evaluate the impact of HIF-PH inhibitors on cardiac function using advanced cardiovascular imaging modalities, including cardiac magnetic resonance imaging. The primary outcome is the haemoglobin level at 16 weeks of randomization, and all adverse events will be recorded and evaluated for any association with daprodustat treatment.
Conclusion: Considering the hypothetical upside and downside of using HIF-PH inhibitors in anaemic patients with HF and chronic kidney disease, and because there are virtually no safe and effective treatments for patients with anaemia not caused by iron deficiency, our study results will contribute significantly to this field.
Keywords: Anaemia; Chronic kidney disease; Daprodustat; HIF-PH inhibitor; Heart failure; Study protocol.
© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.