INFERR-Iron Infusion in Haemodialysis Study: INtravenous Iron Polymaltose for First Nations Patients With High FERRitin Levels On Haemodialysis A Protocol for a Prospective Open-Label Blinded Endpoint Randomised Controlled Trial

Abstract

BackgroundThe effectiveness of erythropoiesis stimulating agents, which are the main stay of managing anaemia of chronic kidney disease (CKD) is largely dependent on adequate body iron stores. The iron stores are determined by the levels of serum ferritin concentration and transferrin saturation. These two surrogate markers of iron stores are used to guide iron replacement therapy. Most Aboriginal and/or Torres Islander Australians of the Northern Territory (herein respectively referred to as First Nation Australians) with end stage kidney disease have ferritin levels higher than current guideline recommendations for iron therapy. There is no clear evidence to guide safe and effective treatment with iron in these patients. We aim to assess the impact of intravenous iron treatment on all-cause death and hospitalisation with a principal diagnosis of all-cause infection in First Nation patients on haemodialysis with anaemia, high ferritin levels and low transferrin saturationMethodsIn a prospective open-label blinded endpoint randomised controlled trial, a total 576 participants on maintenance haemodialysis with high ferritin (>700µg/L and ≤2000µg/L) and low transferrin saturation (<40%) from 7 renal units across the Northern Territory of Australia will be randomised 1:1 to receive intravenous iron polymaltose 400mg once monthly (200mg during 2 consecutive haemodialysis sessions) (Arm A) or no IV iron treatment (standard treatment) (Arm B). Rescue therapy will be administered when the ferritin levels fall below 700µg/L or when clinically indicated. The primary outcome will be the differences between the two-study arms in the risk of hospitalisation with all-cause infection or death. An economic analysis and several secondary and tertiary outcomes analyses will also be performed.DiscussionThe INFERR clinical trial will address significant uncertainty on the safety and efficacy of iron therapy in First Nation Australians with CKD with hyperferritinaemia and evidence of iron deficiency. This will hopefully lead to the development of evidence-based guidelines. It will also provide the opportunity to explore the causes of hyperferritinaemia in First Nation Australians. Trial registrationThis trial is registered with The Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12620000705987; Registered 29 June 2020https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378517