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
Intervention: Saline; Ferinject or CosmoFer
Intervention description: intravenous, no active drug; Intravenous, 1000 mg iron
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 56.0
Sex: All
Minimum age: 16 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Idiopathic pulmonary arterial hypertension (IPAH); Iron deficiency

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
    

Eligibility criteria:

        -  Males or females aged between 16-75 years old

          -  Pulmonary Arterial Hypertension (PAH) which is idiopathic, heritable or associated
             with anorexigens.

          -  Iron deficiency (TfR levels > 28.1 nmol/l, where sTfR analysis is available, Ferritin
             < 37 ug/l; transferrin saturations < 16.4%; iron < 10.3 umol/l)

          -  Documented diagnosis of PAH by right heart catheterisation performed at any time prior
             to Screening showing: resting mean pulmonary artery pressure >25mmHg, pulmonary
             capillary wedge pressure =/< 15 mm Hg and normal or reduced cardiac output;

          -  6 minute walking distance greater than 50m at entry;

          -  Stable on an unchanged PAH therapeutic regime (any combination of endothelin receptor
             antagonist, phosphodiesterase inhibitor or prostacyclin analogue) for at least 1
             month.

          -  Able to provide written informed consent prior to any study-mandated procedures

          -  Female subjects of child-bearing potential are eligible to participate if they agree
             to use one of the following contraception methods:

          -  Abstinence

          -  Contraceptive methods with a failure rate of < 1%:

          -  Oral contraceptive, either combined or progestogen alone;

          -  Injectable progestogen;

          -  Implants of levonorgestrel;

          -  Estrogenic vaginal ring;

          -  Percutaneous contraceptive patches;

          -  Intrauterine device (IUD) or intrauterine system (IUS) that meets the <1% failure rate
             as stated in the product label;

          -  Male partner(s) sterilization (vasectomy with documentation of azoospermia) prior to
             the female subject's entry into the study;

          -  Double barrier method: condom and occlusive cap (diaphragm or cervical/vault caps)
             plus vaginal spermicidal agent (foam/gel/film/cream/suppository).

        Exclusion criteria

          -  Unable to provide informed consent.

          -  Clinically-significant renal disease (Creatinine clearance < 30 ml/min per 1.73 m2
             calculated from Chronic Kidney Disease-Epidemiology Collaboration (CKD-Epi)
             http://www.qxmed.com/renal/Calculate-CKD-EPI-GFR.php) or liver disease (including
             serum transaminases > 3 times upper limit of normal).

          -  Haemoglobin concentration <10 g/dl.

          -  Patients will be excluded if any single parameter (iron, ferritin or transferrin
             saturation) exceeds 1x upper limit of normal (ULN) in the local lab reference range.

          -  Patients with moderate to severe hypophosphatemia as defined as <0.65mmol/L

          -  Known to have haemoglobinopathy e.g. sickle cell disease, thalassaemia.

          -  Admission to hospital related to PAH or change in PAH therapy within 1 month prior to
             Screening.

          -  Evidence of left ventricular disease or significant lung disease on high-resolution
             Computed Tomography (CT) scanning or lung function as judged by the investigator

          -  Acute or chronic infection or inflammation.

          -  Significant uncontrolled asthma as judged by the investigator, eczema or atopic
             allergies.

          -  Females who are lactating or pregnant.

          -  Individuals known to have Human Immunodeficiency Virus (HIV), Hepatitis B or C or
             Creutzfeld-Jakob disease.

          -  Known hypersensitivity to Ferinject® or any of its excipients.

          -  Evidence of disturbances in utilisation of iron.

          -  Significant blood loss (e.g. Gastro-intestinal bleed) within the last 3 months or
             history of menorrhagia.

          -  Unable to perform a Cardiopulmonary Exercise Test i.e. due to syncope or
             musculoskeletal factors.

          -  Patients who have received an investigational medicinal product within 30 days of
             entering the baseline visit