Complications after major surgery are common and decrease survival. Tissue hypoxia is established as a driver of postoperative complications. All complex cells can adapt to low oxygen conditions by activating the highly conserved hypoxia inducible factor (HIF) pathway. Roxadustat is a first-in-class oral prolyl hydroxylase inhibitor that increases HIF signalling, marketed since 2018 for the treatment of anaemia in chronic kidney disease. Brief preoperative Roxadustat exposure stands to prime cells to function well under the anticipated hypoxic stress of major surgery, a clinical insult that is unique due to its precise timing.
The investigators will conduct a pilot study to assess whether a definitive phase 3 randomised controlled trial of preoperative Roxadustat vs placebo in patients undergoing major noncardiac surgery is safe, feasible and justified.
The study will enrol 150 adult patients undergoing major abdominal, orthopaedic or vascular surgery who will be randomly allocated to receive three preoperative doses of oral Roxadustat 100 mg or placebo.
The primary endpoint is any significant acute preoperative illness following first tablet ingestion AND/OR any postoperative complication within 30 days. Secondary endpoints will include biomarker profiles of organ injury and a comprehensive suite of perioperative core outcome measures.
The results of this pilot study will inform the design of a large international trial to test whether Roxadustat reliably improves recovery after major surgery.
Associate Professor Andrew Toner, Professor Tomas Corcoran, Royal Perth Hospital, Western Australia; Professor Cormac Taylor, Conway Institute, University College Dublin, Ireland; Professor Simon Keely, The University of Newcastle and Hunter Medical Research Institute, NSW.
The project was awarded A$70,000 funding through the ANZCA research grants program for 2025.