Effects of intravenous iron therapy with ferric carboxymaltose compared with oral iron

INTERVENTION: Trade Name: Ferinject 50 mg/ml Pharmaceutical Form: Solution for injection/infusion INN or Proposed INN: FERRIC CARBOXYMALTOSE CAS Number: 9007‐72‐1 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 50‐ Pharmaceutical form of the placebo: Solution for injection/infusion Route of administration of the placebo: Intravenous use Trade Name: Ferro sanol 100 mg. Pharmaceutical Form: Capsule, hard INN or Proposed INN: GLYCINE FERROUS SULFATE PENTAHYDRATE COMPLEX Other descriptive name: GLYCINE FERROUS SULFATE PENTAHYDRATE COMPLEX Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Trade Name: Fisiogen Ferro Forte 30 mg. Pharmaceutical Form: Capsule, hard INN or Proposed INN: FERRIC PYROPHOSPHATE CAS Number: 10058‐44‐3 Other descriptive name: FERRIC PYROPHOSPHATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 350‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: Patients with heart failure with preserved ejection fraction ( HFpEF) and iron deficency anemia. Therapeutic area: Diseases [C] ‐ Cardiovascular Diseases [C14] PRIMARY OUTCOME: Main Objective: Assess whether intravenous treatment with iron carboxymaltose or oral treatment (ferroglicina iron sulfate or liposome) in patients with HF Preserved LVEF and iron deficiency anemia, can improve functional capacity measured by the 6‐minute walk (6MWT) test compared to placebo at 30 weeks after the start of treatment. Primary end point(s): Change in 6MWT distance from baseline to Week 24 visit after the start of investigational drug. Secondary Objective: To determine whether IV ferric carboxymaltose improve NYHA class and quality of life (Living; with Heart Failure Minessota questionnaire), and reduce mortality and hospitalizations, in patients with HFpEF in comparison with oral iron. Timepoint(s) of evaluation of this end point: 24 weeks SECONDARY OUTCOME: Secondary end point(s): ‐ Change in NYHA class at Weeks 6, 12, 24 and 30; ‐ Change Kansas City Cardiomyopathy questionnaire (KCCQ to to Weeks 6, 12, 24 and 30; ‐ Rate of any, HF‐related or other cardiovascular hospitalizations.; ‐ Time to the first hospitalization for any reason, for worsening of CHF, other cardiovascular‐related events, or for any cardiovascular reason. Timepoint(s) of evaluation of this end point: Weeks 6, 12, 24 and 30 INCLUSION CRITERIA: 1. Subjects with stable chronic HF (NYHA II/IV functional class) on optimal background therapy (as determined by the investigator) for at least 4 weeks with no dose changes of heart failure drugs during the last 2 weeks (with the exception of diuretics). In general, optimal pharmacological treatment should include an angiotensin‐converting enzyme inhibitor or angiotensin II receptor blocker and a beta blocker unless contraindicated or not tolerated and diuretic if indicated. 2. Left ventricular ejection fraction >45% (value within 3 months of planned date of randomization). 3. BNP >100 pg/mL and/or N‐terminal‐pro‐BNP >400 pg/mL at the screening visit. 4. Subject must be capable of completing the 6MWT. 5. Screening serum ferritin <100 ng/mL or 100–300 ng/mL with transferrin saturation <20%. 6. At least 18 years of age. 7. Before any study‐specific procedure, the appropriate written informed consent must be obtained. Are the trial subjects