title: Supplementation of iron in pulmonary hypertension: Rationale and design of a phase II clinical trial in idiopathic pulmonary arterial hypertension.
abstract: Our aim is to assess the safety and potential clinical benefit of intravenous iron (Ferinject) infusion in iron deficient patients with idiopathic pulmonary arterial hypertension (IPAH). Iron deficiency in the absence of anemia (1) is common in patients with IPAH; (2) is associated with inappropriately raised levels of hepcidin, the key regulator of iron homeostasis; and (3) correlates with disease severity and worse clinical outcomes. Oral iron absorption may be impeded by reduced absorption due to elevated hepcidin levels. The safety and benefits of parenteral iron replacement in IPAH are unknown. Supplementation of Iron in Pulmonary Hypertension (SIPHON) is a Phase II, multicenter, double-blind, randomized, placebo-controlled, crossover clinical trial of iron in IPAH. At least 60 patients will be randomized to intravenous ferric carboxymaltose (Ferinject) or saline placebo with a crossover point after 12 weeks of treatment. The primary outcome will be the change in resting pulmonary vascular resistance from baseline at 12 weeks, measured by cardiac catheterization. Secondary measures include resting and exercise hemodynamics and exercise performance from serial bicycle incremental and endurance cardiopulmonary exercise tests. Other secondary measurements include serum iron indices, 6-Minute Walk Distance, WHO functional class, quality of life score, N-terminal pro-brain natriuretic peptide (NT-proBNP), and cardiac anatomy and function from cardiac magnetic resonance. We propose that intravenous iron replacement will improve hemodynamics and clinical outcomes in IPAH. If the data supports a potentially useful therapeutic effect and suggest this drug is safe, the study will be used to power a Phase III study to address efficacy.
authors: Department of Cardiology, National Pulmonary Hypertension Service, Hammersmith Hospital, London, United Kingdom ; National Heart and Lung Institute, London, United Kingdom.
authors: Luke S G E
authors: LS
authors: Howard
authors: Geoffrey M J
authors: GM
authors: Watson
authors: John
authors: J
authors: Wharton
authors: Christopher J
authors: CJ
authors: Rhodes
authors: Kakit
authors: K
authors: Chan
authors: Rajeshree
authors: R
authors: Khengar
authors: Peter A
authors: PA
authors: Robbins
authors: David G
authors: DG
authors: Kiely
authors: Robin
authors: R
authors: Condliffe
authors: Charlie A
authors: CA
authors: Elliott
authors: Joanna
authors: J
authors: Pepke-Zaba
authors: Karen
authors: K
authors: Sheares
authors: Nicholas W
authors: NW
authors: Morrell
authors: Rachel
authors: R
authors: Davies
authors: Deborah
authors: D
authors: Ashby
authors: J Simon R
authors: JS
authors: Gibbs
authors: Martin R
authors: MR
authors: Wilkins
keywords: exercise capacity; ferric carboxymaltose; iron; pulmonary arterial hypertension; pulmonary vascular resistance
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