Clinical trial NCT06270498: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Chronic Heart Failure
Iron-deficiency
Left Ventricular Systolic Dysfunction
Keywords: heart failure
iron deficiency
sucrosomial iron
Lead sponsor: Azienda Ospedaliero, Universitaria Pisana
Sponsor class: OTHER
Collaborators: name: University of Pisa
First posted: 2024-02-21
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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) \&lt;50%. Iron deficiency was defined as transferrin saturation (TSAT) \&lt;20%.

Eligibility criteria: 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 \&lt;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: \&gt;300 pg/mL (or BNP \&gt;100 pg/mL) for patients in normal sinus rhythm; \&gt;1,000 pg/mL (or BNP \&gt;400 pg/mL) for patients in atrial fibrillation
4. TSAT \&lt;20%
5. Hemoglobin 10.0-15.0 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 (\&lt;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 \&gt;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\&lt;10 g/dL or Hb\&gt;15 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 \&gt;400 ng/mL)
16. Hypersensitivity to any of the study products or known severe allergies
17. Participation in another study
18. Low body weight (\&lt;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)

Primary outcomes:
measure: Exercise capacity
timeFrame: 12 weeks
Secondary outcomes:
measure: Quality of life
timeFrame: 12 weeks
measure: 6MWT distance improvement
timeFrame: 12 weeks
measure: Quality of life improvement
timeFrame: 12 weeks
measure: Exercise capacity (peak oxygen consumption)
timeFrame: 12 weeks
measure: F2-isoprostanes
timeFrame: 12 weeks
measure: Soluble NOX2-derived peptide (sNOX2-dp)
timeFrame: 12 weeks
measure: H2O2
timeFrame: 12 weeks
measure: Phosphate
timeFrame: 12 weeks
measure: Fibroblast growth factor (FGF)-23
timeFrame: 12 weeks
Other outcomes:
measure: N-terminal pro-B-type natriuretic peptide (NTproBNP)
timeFrame: 12 weeks
measure: Transferrin saturation (TSAT)
timeFrame: 12 weeks
measure: Ferritin
timeFrame: 12 weeks
measure: Serum iron
timeFrame: 12 weeks
measure: Soluble transferrin receptor (sTfR)
timeFrame: 12 weeks
measure: Hepcidin
timeFrame: 12 weeks
measure: Cardiac structure and function 1
timeFrame: 12 weeks
measure: Cardiac structure and function 2
timeFrame: 12 weeks
measure: Cardiac structure and function 3
timeFrame: 12 weeks
measure: Cardiac structure and function 4
timeFrame: 12 weeks
measure: Cardiac structure and function 5
timeFrame: 12 weeks
measure: Cardiac structure and function 6
timeFrame: 12 weeks
measure: Clinical outcome
timeFrame: 12 weeks
Locations:
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
state: Toscana
Study officials:
affiliation: University of Pisa
name: Gabriele Masini, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pisa
name: Raffaele De Caterina, MD PhD
role: STUDY_DIRECTOR
References: