IV Iron Replacement for Iron Deficiency in Idiopathic Pulmonary Arterial Hypertension (IPAH) Patients

This study will establish whether intravenous iron replacement has clinical benefit in idiopathic pulmonary arterial hypertension. A 24-week double-blind, randomised, placebo-controlled, crossover study will investigate whether a single dose of 1g of Ferinject® or CosmoFer improves cardiopulmonary haemodynamics, exercise capacity and quality of life and is well-tolerated. IV iron formulation used in Europe - Ferinject IV iron formulation used in China - CosmoFer

These results represent the outcome of two separate clinical trials which were conducted in collaboration, led by Imperial College and Fuwai, China respectively. The protocols were analogous, although in China Endurance Cardio-Pulmonary Exercise Testing (CPET) was not done and instead of Ferinject/Placebo being infused over 15 minutes, Cosmofer/Placebo was infused over 4-6 hours. The study analyses were performed as Intention to Treat, except for patients 6009-6017 as described below. The study was a cross-over design and results are presented for 2 groups based on the participants' study timepoint, and presented separately for the two study datasets (Europe and Fuwai). A meta-analysis was conducted for the combined data where possible and the relevant p-values have been provided. Iron results in the European dataset are taken from blood results which were collected centrally and analysed by one laboratory at Imperial College London. N-Terminal B-type natriuretic peptide (NT-PRO-BNP) and Soluble Transferrin Receptors (STFR) were not done at Fuwai. The study was conducted according to Good Clinical Practice (GCP), but there were some missing data (imputed using multiple imputation techniques), and also some significant protocol deviations which are summarised below. Six participants (2003, 3004, 4002-4005) had their endurance CPETs set at incorrect workloads which differed significantly from that achieved at the baseline incremental CPET. These data were therefore treated as missing, and relevant values imputed as per the statistical analysis plan. Visit 5 CPETs for participants 1008 (Incremental CPET 12 weeks later) 1018 (Endurance CPET 13 days later) and 1019 (Incremental CPET 15 days later) were performed outside the protocol-specified window. Participant 1014 received placebo at both treatment visits in error. Participant 6017 suffered a suspected allergic reaction to their first infusion and was withdrawn from the study. There was a systemic error where participants 6009-6016 received the opposite to their random-assigned treatment at each time point. These participants were analysed according to the treatment actually received, rather than that originally assigned by randomisation.