About this trial
The primary objective of this study is to determine if the correction of functional iron deficiency by administering a single dose of intravenous iron (ferric derimaltose or Monoferric®) in participants with heart failure with preserved ejection fraction (HFpEF) will improve exercise capacity as measured by the change in peak oxygen uptake (peak VO2) from baseline to 12 weeks.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Adult (≥18 years of age) able to provide informed consent.
Stable heart failure (NYHA II-IV) for at least 4 weeks
Heart Failure with Preserved left ventricular ejection fraction.(Left ventricular ejection fraction ≥ 50 % obtained within 6 months of informed consent.
NT-proBNP ≥ 125 pg/mL without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at the time of sample collection, NT-proBNP must be ≥ 250 pg/mL OR patients must have a history of pulmonary capillary wedge pressure ≥ 15 mm Hg during rest or the slope of pulmonary capillary wedge pressure to cardiac output (PCWP/CO) ≥ 2.0 mmHg/L/min during upright exercise (Eisman et al., Circ Heart Fail. 2018 May;11(5):e004750.).OR subjects must have a heart failure hospitalization within the last 12 months prior to screening OR Chronic diastolic dysfunction on echocardiography as evidenced by: Left Atrial Enlargement (LAE): LA diameter ≥ 3.8cm in women, ≥ 4.0 cm in men or LA length ≥ 5.0 cm or LA area ≥ 20 cm2 OR LA volume ≥ 55mL or LA volume index ≥ 29ml/m2 or Left Ventricular Hypertrophy (LVH): septal thickness or posterior wall thickness ≥ 1.1 cm OR For patients in sinus rhythm: E/e' ratio ≥15 at septal annulus, or E/e' ratio ³13 at lateral annulus, or average E/e' ratio ³14. For patients in atrial fibrillation: E/e' ≥ 11 at the septal annulus.
Disqualifiers
Current or planned intravenous iron supplementation. Iron-containing multivitamins (<30 mgs /day) are permitted.
Known hypersensitivity reaction to any component of ferric derisomaltose (Monofer®)
History of acquired iron overload (e.g. hemochromatosis), or the recent receipt (within 3 months) of erythropoietin stimulating agent, IV iron therapy, or blood transfusion.
Documented active gastrointestinal bleeding
Trial design
Parallel
Treatments tested in this trial
Ferric Derisomaltose 1000 Mg in 100 mL INTRAVENOUS SOLUTION [Monoferric]
DrugFerric derisomaltose (Monoferric) 1000 mg X1 (for subject \<50 kg, 20 mg/kg
Placebo
DrugNormal saline
Treatment groups
Trial outcomes
Primary outcomes
The change in peak oxygen uptake (peak VO2) from baseline to week 12 in HFpEF subjects with functional iron deficiency following a single dose of ferric derisomaltose or placebo.
Peak VO2 measured by a maximal effort Cardiopulmonary Exercise Test (CPET)
Secondary outcomes
Change in resting pulmonary capillary wedge pressure (PCWP)
Measured by right heart catheterization with CPET
Change in resting pulmonary artery pressure (PAP)
Measured by right heart catheterization with CPET
Change in exercise pulmonary capillary wedge pressure/ cardiac output slope (PCWP/CO slope)
Measured by right heart catheterization with CPET
Change in exercise pulmonary arterial pressure/ cardiac output slope (PAP/CO slope)
Measured by right heart catheterization with CPET
Sponsors and contacts
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Massachusetts General Hospital
Lead sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator
Pharmacosmos A/S
Collaborator
National Institutes of Health (NIH)
Collaborator