P0858A MULTICENTRE PROSPECTIVE DOUBLE BLIND RANDOMISED CONTROLLED TRIAL OF INTRAVENOUS IRON IN IRON DEFICIENT BUT NOT ANAEMIC PATIENTS WITH CHRONIC KIDNEY DISEASE ON FUNCTIONAL STATUS
Authors: Kassianides Xenophon , Ziedan Ahmed , Allgar Victoria , Lamplugh Archie , Kalra Philip A , Macdougall Iain , Bhandari Sunil 
Published: June 2020

Background and Aims

Iron deficiency is common in patients with CKD due to inadequate dietary intake of iron, poor iron absorption from the gut, and increased iron losses from the body. In addition to preventing anaemia, iron is also important for normal heart function, being involved in processes that generate a necessary continuous energy supply. Post hoc analysis of studies of people with iron deficiency and advanced CKD suggest treatment with intravenous iron leads to improvement in heart function and feeling of wellbeing.

The aim of the study was to investigate whether intravenous (IV) iron could improve exercise capacity in comparison to placebo over 3 months in non-anaemic CKD patients who have iron deficiency.

Method

The Iron and the Heart Study was a prospective double blinded explorative randomized, multi-centre study designed to assess the effect of IV iron supplementation (ferric derisomaltose/iron isomaltoside 1000 (FDI); Monofer®) in iron deficient but not anaemic patients with advanced CKD on functional status. Adults with established CKD stages 3b-5 and serum ferritin (SF) &lt; 100mcg/L and/or transferrin saturation (TS) &lt;20% were randomized in a 1:1 ratio to 1000 mg IV FDI or placebo solution. Each participant was followed up at months 1 and 3. The primary outcome was the difference in exercise capacity using the 6-minute walk test (6MWT) at 3 months. Secondary objectives included effects on haematinic profiles and haemoglobin (Hb) concentrations. Results are given as mean and standard deviations (SD). Data was analysed using ANCOVA adjusted for baseline.

Results

Between October 2016 and April 2018, 54 individuals from 3 UK centres were randomized to FDI (n=26; mean age 61.6 (10.1) years) or placebo (n=28; mean age 57.8 (12.9) years). Mean serum creatinine (167.0 (40.2) vs. 204.9 (67.3) and eGFR (32.1 (9.6) vs. 29.1 (9.6)) at baseline were similar in FDI and placebo groups respectively. Adjusting for baseline 6MWT, the 6MWT at 1-month showed no statistically significant difference between groups (p=0.736) (Figure), and no significant difference at 3 months (p=0.741). The absolute mean change from baseline to 1 month and 3 months, showed no statistically significant differences between group (p=0.952_, p=0.895). There was no statistically significant difference between groups in Hb at 3-months (p=0.152) but there were statistically significant differences in SF and TS, which both increased post FDI infusion at 1 and 3 months; p&lt;0.001 (Table).

Conclusion

The Iron and the Heart Trial showed a significant increase in iron parameters and maintenance of Hb concentration in iron treated patients. There was a numerical increase in functional capacity at 1-month and to lesser extent at 3 months post iron infusion. This finding was not significant, which reflects the limited sample size and possible differences in population during randomisation with the large difference in 6MWT at baseline. A larger study will be required to demonstrate a possible short-term functional benefit on exercise capacity of IV iron in CKD patients with biochemical functional or absolute iron deficiency without anaemia.