Effect of IV Iron in Patients With Heart Failure With Preserved Ejection Fraction

Prior treatment

• Use of IV iron, erythropoietin or blood transfusions within the previous 60 days;
• Use of concurrent immunosuppressive therapy;
• Renal replacement therapy;
• Concurrent therapy with an erythropoiesis stimulating agent;
• Participation in another clinical trial within previous 30 days and/ or anticipated participation in another trial during this study.

Other illness

• Clinical signs and symptoms of infection including fever \>38°C;
• History of acquired iron overload or haemochromatosis (or a first relative with haemochromatosis);
• Known hypersensitivity to FCM or any other IV iron product;
• Known bleeding or haemolytic anemia;
• Presence of any condition that precludes exercise testing, such as decompensated HF, significant musculoskeletal disease, unstable angina pectoris, obstructive cardiomyopathy, severe uncorrected valvular disease, or uncontrolled brady-arrhythmias or tachy-arrhythmias;
• Probable alternative diagnoses that in the opiniton of the investigator could account for the patient's HF symptoms such as severe obesity, primary pulmonary hypertension, or chronic obstructive pulmonary disease (COPD); hence, patients with the following are excluded:
  • Severe COPD, i.e. with known FEV1 \<50%, requiring home oxygen therapy, or on chronic oral steroid therapy;
  • body mass index ≥40.0 kg/m2;
• Presence of uncontrolled atrial fibrillation with resting heart rate \>110/min;
• Presence of uncontrolled hypertension with blood pressure \>160/100 mm Hg;
• Known active malignancy;
• Known HIV or active hepatitis infection;
• Lack of willingness to storage and disclosure of pseudonymous disease data in the context of the clinical trial.

Lab values

• Any prior echocardiography measurement of LVEF \<40%;

Other

• Unable to sign informed consent
• Pregnancy;
• Patients, who may be dependent on the sponsor, the investigator or the trial sites, have to be excluded from the trial
• Inability to fully comprehend and/or perform study procedures in the investigator's opinion;
• Persons staying at an institution due to order by a national body or a court of law.

• Patient is willing to participate and provides written informed consent;
• Age ≥18 years;
• Clinical diagnosis of heart failure with preserved ejection fraction (HFpEF) with LVEF ≥45% at screening or within 6 months prior to planned randomisation (assessed by echocardiography or MRI);
• Ambulatory for at least 7 days with NYHA class II or III at time of randomisation (the screening visit can take place at the end of a hospitalisation);
• Treated with a diuretic;
• Presence of atrial fibrillation (AF) at screening or randomisation is allowed in 2 out of 4 patients (calculated per centre);
• At screening or randomisation, presence of one of the following criteria:
  • hospitalisation with a diagnosis of HF within 12 months prior to planned randomisation; OR
  • raised plasma levels of natriuretic peptides in a patient with sinus rhythm (i.e. in patients without AF: NT-proBNP \>300 pg/mL or BNP \>100 pg/mL or MR-proANP \>120 pmol/L; in patients with AF: NT-proBNP \>600 pg/mL or BNP \>200 pg/mL or MR-proANP \>250 pmol/l)
• Evidence of diastolic dysfunction at screening or randomisation, defined as:
  • E/E' \>13; OR
  • LA width ≥38 mm; OR
  • LA length ≥50 mm; OR
  • LA area ≥20 cm2; OR
  • LA volume ≥55 ml; OR
  • left atrial volume index \>28 mL/m2;
• Haemoglobin \>9.0 g/dL and ≤14.0 g/dL (at screening);
• ID with ferritin \<100 ng/mL or ferritin 100-299 plus TSAT \<20% (at screening);
• 6-minute-walking distance at baseline \<450 m (average of the last 2 documented tests within 8 weeks prior to planned randomisation that also need to be within 20% of each other).