Protocol Version 2.2 to 3.0 (approved 05/07/2018): • Eligibility expanded to include all patients with LVEF </= 45% irrespective of degree of symptoms (NYHA class). • Removal of need to quantify mRNA levels as excessive work given that protein levels will be measured. • Change in comparison time for the iron absorption test from 2 to3 days. • Removal of ‘change in’ for the endpoints and safety evaluation and using ‘week 12’ measurements as endpoints and ‘Serum iron level at 3 hours after oral’ drug, in case of iron absorption test. • Removal of alanine transaminase from liver function test list as King’s College Hospital does not measure it routinely. • Clarification that only folate and vitamin B12 levels below the lower limit of normal were an exclusion criteria as levels above the upper limit are not physiological adverse. • Removal of cellular energetic status from the blood tests as will not be an endpoint due to it not being needed and FACS machine out of service. GLOBIFER-HF CLINICAL STUDY REPORT 10 • Clarification that chronic lung disease would only be a contraindication if patients had objective measures of severe lung disease (FEV1<50% predicted). • Removal of chronic renal impairment with eGFR <45 as an exclusion criterion, and relaxing eGFR<30 from <65 in diabetics. • Adding ‘planning to get pregnant’ to exclusion criteria. • Clarification that functional valvular disease will bot be a contraindication.

Protocol Version 3.1 to 4.0 (approved 19/06/2019): • Removal of stratification of study size into groups absolute or functional iron deficiency. • Removal of testing of Haem-carrier protein 1, and haem regulatory gene 1 from the in vitro iron transporter studies. • Change total number of in vitro transporter studies to first 30 randomised patients from first 20 of each strata. • Removal of allergic disorders from the exclusion criteria. • Additional of oral haemoglobin preparations use as an exclusion criterion. • Change of compliance check telephone calls from weeks to 2 weekly • Removal of IL-10, and gamma interferon from the cytokine assay list.

Protocol Version 4.0 to 5.0 (approved 07/07/2020): • Removal of soluble transferrin receptor as a baseline and end of study visit blood test • Removal of TNF receptor 1&2 from the cytokine list. • Cytokines and Hepcidin-25 ELISA measurements will be outsourced to Affinity Biomarker Labs rather than be performed in King’s College BHF Centre.