Effects of Iron Therapy in Heart Failure With Preserved Ejection Fraction and Iron Deficiency (PREFER-HF)

Inclusion Criteria:

• Subjects with stable chronic HF (NYHA II/IV functional class) on optimal backgroundtherapy (as determined by the investigator) for at least 4 weeks with no dosechanges of heart failure drugs during the last 2 weeks (with the exception ofdiuretics). In general, optimal pharmacological treatment should include anangiotensin-converting enzyme inhibitor or angiotensin II receptor blocker and abeta blocker unless contraindicated or not tolerated and diuretic if indicated.

• Left ventricular ejection fraction >45% (value within 3 months of planned date ofrandomization).

• BNP >100 pg/mL and/or N-terminal-pro-BNP >400 pg/mL at the screening visit.

• Subject must be capable of completing the 6 minute walking test

• Screening serum ferritin <100 ng/mL or 100-300 ng/mL with transferrin saturation <20%.

• At least 18 years of age.

• Before any study-specific procedure, the appropriate written informed consent mustbe obtained.

Exclusion Criteria:

• Subject has known sensitivity to any of the products to be administered duringdosing.

• History of acquired iron overload.

• History of erythropoietin-stimulating agent, i.v. iron therapy, and/or bloodtransfusion in previous 6 weeks prior torandomization.

• Oral iron therapy at doses >100 mg/day in previous 1 week prior to randomization.Note: ongoing use of multivitamins containing iron <75 mg/day is permitted.

• Exercise training programme(s) in the 3 months prior to screening or planned in thenext 6 months.

• Known active bacterial infection.

• Chronic liver disease (including active hepatitis) and/or screening alaninetransaminase or aspartate transaminase above three times the upper limit of thenormal range.

• Subjects with known hepatitis B surface antigen positivity and/or hepatitis C virusribonucleic acid positivity.

• Vitamin B12 and/or serum folate deficiency. If deficiency-corrected subject may berescreened for inclusion.

• Subjects with known seropositivity to human immunodeficiency virus.

• Clinical evidence of current malignancy with exception of basal cell or squamouscell carcinoma of the skin, and cervical intraepithelial neoplasia.

• Currently receiving systemic chemotherapy and/or radiotherapy.

• Renal dialysis (previous, current, or planned within the next 6 months).

• Unstable angina pectoris as judged by the investigator; severe valvular or leftventricular outflow obstruction disease needing intervention; atrialfibrillation/flutter with a mean ventricular response rate at rest >100 beats perminute.

• Acute myocardial infarction or acute coronary syndrome, transient ischemic attack,or stroke within the last 3 months prior to randomization.

• Coronary artery bypass graft, percutaneous intervention (e.g. cardiac,cerebrovascular, and aortic; diagnostic catheters are allowed), or major surgery,including thoracic and cardiac surgery, within the last 3 months prior torandomization.

• Subject currently is enrolled in or has not yet completed at least 30 days sinceending other investigational device or drug study(ies), or subject is receivingother investigational agent(s).

• Subject of childbearing potential who is pregnant (e.g. positive human chorionicgonadotropin test) or is breastfeeding.

• Subject will not be available for all protocol-specified assessments.

• Subject has any kind of disorder that compromises the ability of the subject to givewritten informed consent and/or to comply with study procedures.