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

Phase 4

Recruiting

• Conditions: Chronic Heart Failure; Iron-deficiency; Left Ventricular Systolic Dysfunction

• Registration Number: NCT06270498
• Lead Sponsor: Raffaele De Caterina

Brief Summary

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%.

Study Timeline

• Study First Submitted: 2024-02-10
• Study First Submitted QC: 2024-02-19
• Study First Posted: 2024-02-21
• Study Start: 2024-03-14
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-25
• Last Update Posted: 2025-10-01
• Primary Completion: 2026-03-14
• Study Completion: 2026-06-14

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. 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
2. LVEF<50% at screening visit (historical value can be used if performed within 6 months of screening visit)
3. 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
4. TSAT <20%
5. Hemoglobin 10.0-16.0 g/dL
6. 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)
7. Age ≥18 years, male and female
8. Willingness to provide informed consent
9. Subjects who decide to use single or dual contraceptive methods to avoid conceiving during the study period

Exclusion Criteria

1. Neuromuscular, orthopedic or other non-cardiac condition that prevents the patient from exercise testing
2. Exercise training program in the previous 3 months, or planned in the next 3 months
3. Recent (<3 month) acute coronary syndrome, coronary artery bypass surgery, percutaneous coronary interventions, transient ischemic attack, or stroke
4. Severe valvular disease, hypertrophic obstructive cardiomyopathy, restrictive or constrictive cardiomyopathy, acute myocarditis
5. Atrial fibrillation or flutter with a ventricular response rate of &gt;100 beats per minute at rest
6. Temperature ≤38 °C (oral or equivalent) or active infection as defined by current use of oral or intravenous antimicrobial agents
7. Need for blood transfusion within the last month
8. Hb<10 g/dL or Hb>16 g/dL
9. Rapid iron repletion with intravenous iron is considered a clinical necessity by physicians after reviewing patient medical record
10. Documented active gastrointestinal bleeding
11. Oral iron, i.v. iron or erythropoietin stimulating agent within the last 3 months
12. eGFR ≤15 mL/min or on hemodialysis
13. Chronic liver disease and/or alanine transaminase or aspartate transaminase above 3 times the upper limit of the normal range
14. Active cancer
15. Evidence of iron overload (ferritin >400 ng/mL)
16. Hypersensitivity to any of the study products or known severe allergies
17. Participation in another study
18. Low body weight (≤35 kg)
19. Known or anticipated pregnancy in the next 4 months
20. Need for forbidden medications
21. Breastfeeding
22. Consumption of iron-rich foods or any food that alter iron absorption (i.e. food rich in vitamin C) due to dietary requirements
23. 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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Difference in six-minute walk test (6MWT) distance, expressed as meters	12 weeks
Difference in Kansan City Cardiomyopathy Questionnaire (KCCQ)-12 overall score	12 weeks

Secondary Outcome Measures

Name	Time	Method
Proportion of patients with 15 meters improvement in 6MWT distance (responders)	24 weeks
Proportion of patients with 5-point improvement in KCCQ-12 score (responders)	24 weeks
Difference in six-minute walk test (6MWT) distance, expressed as meters	24 weeks
Difference in Kansan City Cardiomyopathy Questionnaire (KCCQ)-12 overall score	24 weeks
Bone metabolism indices	24 weeks	Change in phosphate and FGF-23
Iron indices	24 weeks	Change in TSAT, ferritin and serum iron
Oxidative stress	24 weeks	Change in F2-isoprostanes, Soluble NOX2-derived peptide and H2O2
Iron indices 2	24 weeks	change in soluble receptor of transferrin and hepcidin
Systolic cardiac function	24 weeks	Change in left ventricular ejection fraction, %
NTproBNP	24 weeks	Change in NT-proBNP
Clinical events	24 weeks	Time to death or to first HF hospitalization
Left atrial volume	24 weeks	Change in left atrial volume
Left ventricular volume	24 weeks	Change in left ventricular end-diastolic volume
Left ventricular diastolic function	24 weeks	change in E/e' ratio
Echocardiographic estimation of pulmonary pressure	24 weeks	change in systolic pulmonary artery pressure

Trial Locations

Locations (1)

Azienda Ospedaliero Universitaria Pisana; 🇮🇹 Pisa, Tuscany, Italy