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

Official title

Effect of Oral sucRosomIal Iron on exerciSE Capacity and Quality of Life in Patients With Heart Failure: a Randomized, Placebo-controlled Trial (RISE-HF)

Overview

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.

Detailed description

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%.

Interventions

• Dietary supplement Sucrosomial iron
  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
• Other Placebo
  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.

Primary outcome measures

• Difference 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]

Secondary outcome measures (12)

• 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 [Time frame: 12 weeks]
• Bone metabolism indices [Time frame: 24 weeks]
• Iron indices [Time frame: 12 weeks]
• Iron indices [Time frame: 24 weeks]
• Oxidative stress [Time frame: 12 weeks]
• Oxidative stress [Time frame: 24 weeks]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• Neuromuscular, orthopedic or other non-cardiac condition that prevents the patient from exercise testing
• Exercise training program in the previous 3 months, or planned in the next 3 months
• 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
• Atrial fibrillation or flutter with a ventricular response rate of \&gt;100 beats per minute at rest
• Temperature ≤38 °C (oral or equivalent) or active infection as defined by current use of oral or intravenous antimicrobial agents
• Need for blood transfusion within the last month
• Hb<10 g/dL or Hb>16 g/dL
• Rapid iron repletion with intravenous iron is considered a clinical necessity by physicians after reviewing patient medical record
• Documented active gastrointestinal bleeding
• Oral iron, i.v. iron or erythropoietin stimulating agent within the last 3 months
• 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
• Active cancer
• Evidence of iron overload (ferritin >400 ng/mL)
• Hypersensitivity to any of the study products or known severe allergies
• Participation in another study
• Low body weight (≤35 kg)
• Known or anticipated pregnancy in the next 4 months
• Need for forbidden medications
• Breastfeeding
• Consumption of iron-rich foods or any food that alter iron absorption (i.e. food rich in vitamin C) due to dietary requirements
• 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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Italy · 1 center

• Azienda Ospedaliero Universitaria Pisana — Pisa

Identifiers

NCT: NCT06270498 · 24811

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗