IV Iron Replacement for Iron Deficiency in Idiopathic Pulmonary Arterial Hypertension (IPAH) Patients
Condition: Pulmonary Arterial Hypertension; Iron Deficiency
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension; Anemia, Iron-Deficiency; Iron Deficiencies
Study type: Interventional
Phase: Phase 2

Summary: 
      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
    

Detailed description: 
      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.
    

Intervention name(s): Saline; Ferinject or CosmoFer
Intervention type(s): Drug; Drug
Intervention description(s): intravenous, no active drug; Intravenous, 1000 mg iron
Other intervention name(s): Placebo; Intravenous Iron
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Idiopathic pulmonary arterial hypertension (IPAH); Iron deficiency