The goal of this study is to investigate the effect of oral sucrosomial iron on exercise capacity and quality of life in patients with heart failure (HF) and iron deficiency (ID). The main question the study aims to answer is whether oral sucrosomial iron improved exercise capacity, assessed by six-minute walk test, and quality of life, assessed by Kansas City Cardiomyopathy Questionnaire, compared with placebo. One group of participants will receive treatment with oral sucrosomial iron and the other group will receive treatment with placebo.
Based on clinical trials, treatment with intravenous iron improves symptoms, exercise capacity, and may reduce HF hospitalizations in patients with HF and ID. On the contrary, treatment of ID with oral iron has no effect on exercise capacity. High hepcidin levels prevent oral intestinal absorption and blunt the response to oral iron administration. Sucrosomial iron (SI) consists of a nucleus of ferric pyrophosphate with an envelope of sucrose ester of fatty acids, which promotes intestinal absorption through paracellular and lymphatic routes, independent of hepcidin. In contrast with intravenous iron infusion, administration of oral iron may not promote oxidative stress, since the intestinal iron absorption prevent the formation of labile, non-transferrin bound, plasma iron. The study will investigate the effect of oral SI supplementation on exercise capacity, assessed by six-minute walk test, and quality of life, assessed by Kansas City Cardiomyopathy Questionnaire, compared with placebo in patients with HF, a left ventricular ejection fraction (LVEF) \<50%. Iron deficiency was defined as transferrin saturation (TSAT) \<20%.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
60
Sucrosomial iron with the addition at a fixed dose of vitamin C to promote iron absorption (SiderAL® Forte) will be administered orally once a day for 24 weeks. The dose regimen for all participants will be calculated according to the haemoglobin (Hb) levels at baseline evaluation and to patient's body weight as follows: Hb 14-16 g/dL: 1 tablet once a day, corresponding to 30 mg/daily, for 24 weeks; Hb 10-13.9 g/dL: 2 tablets once a day, corresponding to 60 mg/daily, for 24 weeks
Placebo pills will be identical in shape, form and color of SI tablets; they will contain the same components of SiderAL Forte® except for sucrosomial iron and vitamin C. Placebo will be administered orally once a day for 3 months according to the same dose scheme in the intervention arm.
Azienda Ospedaliero Universitaria Pisana
Pisa, Tuscany, Italy
RECRUITINGDifference in six-minute walk test (6MWT) distance, expressed as meters
Time frame: 12 weeks
Difference in Kansan City Cardiomyopathy Questionnaire (KCCQ)-12 overall score
Time frame: 12 weeks
Proportion of patients with 15 meters improvement in 6MWT distance (responders)
Time frame: 12 weeks
Proportion of patients with 5-point improvement in KCCQ-12 score (responders)
Time frame: 12 weeks
Difference in six-minute walk test (6MWT) distance, expressed as meters
Time frame: 24 weeks
Difference in Kansan City Cardiomyopathy Questionnaire (KCCQ)-12 overall score
Time frame: 24 weeks
Proportion of patients with 15 meters improvement in 6MWT distance (responders)
Time frame: 24 weeks
Proportion of patients with 5-point improvement in KCCQ-12 score (responders)
Time frame: 24 weeks
Bone metabolism indices
Change in phosphate and FGF-23
Time frame: 12 weeks
Bone metabolism indices
Change in phosphate and FGF-23
Time frame: 24 weeks
Iron indices
Change in TSAT, ferritin and serum iron
Time frame: 12 weeks
Iron indices
Change in TSAT, ferritin and serum iron
Time frame: 24 weeks
Oxidative stress
Change in F2-isoprostanes, Soluble NOX2-derived peptide and H2O2
Time frame: 12 weeks
Oxidative stress
Change in F2-isoprostanes, Soluble NOX2-derived peptide and H2O2
Time frame: 24 weeks
Iron indices 2
change in soluble receptor of transferrin and hepcidin
Time frame: 12 weeks
Iron indices 2
change in soluble receptor of transferrin and hepcidin
Time frame: 24 weeks
Systolic cardiac function
Change in Left ventricular ejection fraction, %
Time frame: 12 weeks
Systolic cardiac function
Change in left ventricular ejection fraction, %
Time frame: 24 weeks
NTproBNP
Change in NT-proBNP
Time frame: 12 weeks
NTproBNP
Change in NT-proBNP
Time frame: 24 weeks
Clinical events
Time to death or to first HF hospitalization
Time frame: 12 weeks
Clinical events
Time to death or to first HF hospitalization
Time frame: 24 weeks
Left atrial volume
Change in left atrial volume
Time frame: 12 weeks
Left ventricular volume
Change in left ventricular end-diastolic volume
Time frame: 12 weeks
Left ventricular diastolic function
change in E/e' ratio
Time frame: 12 weeks
Echocardiographic estimation of pulmonary pressure
change in systolic pulmonary artery pressure
Time frame: 12 weeks
Left atrial volume
Change in left atrial volume
Time frame: 24 weeks
Left ventricular diastolic function
change in E/e' ratio
Time frame: 24 weeks
Echocardiographic estimation of pulmonary pressure
change in systolic pulmonary artery pressure
Time frame: 24 weeks
Left ventricular volume
Change in left ventricular end-diastolic volume
Time frame: 24 weeks
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