A study of the short-term effects of oral Roxadustat in volunteers over the age of 40.

Roxadustat is a first-in-class oral prolyl hydroxylase inhibitor, marketed since 2019 exclusively for the treatment of anaemia in chronic kidney disease. Roxadustat increases hypoxia inducible factor (HIF) signalling, the primary mediator of the body’s normal adaptive response to low oxygen levels. HIF is a transcription factor that influences the expression of over 400 genes relating to energy production when oxygen is scarce (glycolysis), improved tissue oxygen delivery (erythropoiesis and angiogenesis), cell survival under stress and enhanced innate immunity. All of these biological mechanisms play a key role in favourable outcomes after the tissue injury of major surgery and the associated stress response. The HYPE Pilot Study (RGS0000006528, SMHS HREC, ACTRN12624000188538) is a separately registered double-blind phase 2 RCT that is currently recruiting at Royal Perth Hospital to explore the safety and potential benefit of three preoperative doses of Roxadustat 100mg in patients undergoing major noncardiac surgery. It remains unclear to what extent such brief Roxadustat exposure changes gene expression in the key pathways outlined above. The HYPE Volunteer Study (RGS0000007340, Central HREC) will complement the HYPE Pilot Study by improving understanding in this area i.e. will potentially substantiate any clinical effects observed in the HYPE Pilot Study and may support a subsequent phase 3 trial.