Effect of Oral sucRosomIal Iron on exerciSE Capacity and Quality of Life in Patients With Heart Failure

Prior treatment

• Exercise training program in the previous 3 months, or planned in the next 3 months
• Need for forbidden medications
• Any pathological condition or disease associated with a reduction or an impairment of intestinal iron absorption (i.e., prior gastrectomy, atrophic gastritis, bariatric surgery, coeliac disease)

Other illness

• Neuromuscular, orthopedic or other non-cardiac condition that prevents the patient from exercise testing
• Recent (\<3 month) acute coronary syndrome, coronary artery bypass surgery, percutaneous coronary interventions, transient ischemic attack, or stroke
• Severe valvular disease, hypertrophic obstructive cardiomyopathy, restrictive or constrictive cardiomyopathy, acute myocarditis
• Temperature ≤38 °C (oral or equivalent) or active infection as defined by current use of oral or intravenous antimicrobial agents
• Documented active gastrointestinal bleeding
• Active cancer
• Hypersensitivity to any of the study products or known severe allergies

Lab values

• Hb\<10 g/dL or Hb\>16 g/dL
• eGFR ≤15 mL/min or on hemodialysis
• Chronic liver disease and/or alanine transaminase or aspartate transaminase above 3 times the upper limit of the normal range

Other

• Atrial fibrillation or flutter with a ventricular response rate of \&gt;100 beats per minute at rest
• Need for blood transfusion within the last month
• Rapid iron repletion with intravenous iron is considered a clinical necessity by physicians after reviewing patient medical record
• Oral iron, i.v. iron or erythropoietin stimulating agent within the last 3 months
• Evidence of iron overload (ferritin \>400 ng/mL)
• Participation in another study
• Low body weight (≤35 kg)
• Known or anticipated pregnancy in the next 4 months
• Breastfeeding
• Consumption of iron-rich foods or any food that alter iron absorption (i.e. food rich in vitamin C) due to dietary requirements

• Chronic HF (New York Heart Association \[NYHA\] functional class II-IV) patients, on optimal therapy, and clinically stable for at least 4 weeks with no dose changes of HF drugs
• LVEF\<50% at screening visit (historical value can be used if performed within 6 months of screening visit)
• Either a documented hospitalization for HF in the previous 12 months of enrolment or an elevated NT-proBNP: ≥250 pg/mL (or BNP ≥75 pg/mL) for patients in normal sinus rhythm; ≥1,000 pg/mL (or BNP ≥400 pg/mL) for patients in atrial fibrillation
• TSAT \<20%
• Hemoglobin 10.0-16.0 g/dL
• Rapid iron repletion with intravenous iron is not considered a clinical necessity by physicians after reviewing patient medical record (if anaemia is present, its grade is no more than mild)
• Age ≥18 years, male and female
• Willingness to provide informed consent
• Subjects who decide to use single or dual contraceptive methods to avoid conceiving during the study period