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.