Randomized Placebo-controlled Trial of FCM as Treatment for Heart Failure With Iron Deficiency / and Sub-Study

Inclusion Criteria

• Adult (≥18 years of age) able to provide signed, written informed consent.
• Stable heart failure (NYHA II-IV) on maximally-tolerated background therapy (as determined by the site Principle Investigator) for at least 2 weeks prior to randomization.
• Able and willing to perform a six-minute walk test (6MWT) at the time of randomization.
• Reduced left ventricular ejection fraction. Assessment must be performed at least 12 weeks after major cardiac surgical intervention including coronary artery bypass graft (CABG), valvular repair/replacement, or cardiac resynchronization therapy (CRT) device implantation.

a. Left ventricular ejection fraction ≤ 40% obtained during the screening visit OR either of the following i. Historical value of ejection fraction ≤ 40% within 24 months of screening visit ii. Historical value of ejection fraction ≤ 30% within 36 months of screening visit

• Hemoglobin >9.0 g/dL and 600 pg/mL (or BNP >200 pg/mL) . b . For patients in atrial fibrillation: NT-proBNP >1000 pg/mL (or BNP >400 pg/mL) .

Exclusion Criteria

• Known hypersensitivity reaction to any component of FCM.
• History of acquired iron overload, or the recent receipt (within 3 months) of erythropoietin stimulating agent, IV iron therapy, or blood transfusion.
• Acute myocardial infarction, acute coronary syndrome, transient ischemic attack, or stroke within 30 days of enrollment.
• Uncorrected severe aortic stenosis, severe valvular regurgitation (except mitral regurgitation due to left ventricular dilatation without planned intervention), or left ventricular outflow obstruction requiring intervention.
• Current atrial fibrillation or atrial flutter with a mean ventricular response rate >100 per minute (at rest).
• Current or planned mechanical circulatory support or heart transplantation.
• Hemodialysis or peritoneal dialysis (current or planned within the next 6 months).
• Documented liver disease, or active hepatitis (i.e. alanine transaminase or aspartate transaminase >3 times the upper limit of normal range).
• Current or recent (within 3 years) malignancy with exception of basal cell carcinoma or squamous cell carcinoma of the skin, or cervical intraepithelial neoplasia.
• Active gastrointestinal bleeding.
• Female participant of child-bearing potential who is pregnant, lactating, or not willing to use adequate contraceptive precautions during the study and for up to 5 days after the last scheduled dose of study medication.
• Inability to return for follow up visits within the necessary windows
• Concurrently in a study with investigational product.
• No participants with Current Coronavirus Disease-19 (COVID-19) Infection into the study.