Chronic Heart FailurePhase 4RISE-HFNCT06270498
Effect of Oral sucRosomIal Iron on exerciSE Capacity and Quality of Life in Patients With Heart Failure
A Phase 4 study testing Sucrosomial iron in people with Chronic Heart Failure and Iron-deficiency, run by Raffaele De Caterina at 1 site in Italy.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Heart Failure, Iron-deficiency, Left Ventricular Systolic Dysfunction
- What is being tested?
- Sucrosomial iron
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteItaly
- Study dates
- 14 Mar 2024to 14 Jun 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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 \>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
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- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Azienda Ospedaliero Universitaria Pisana
Pisa, Tuscany, 56124
Gabriele Masini, MD, PhD
SImona Chiusulo, MD, PhD
About this study
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)
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.
Read the 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%.
- Being tested
- Sucrosomial iron, Placebo
- Keywords
- heart failure, iron deficiency, sucrosomial iron
- Medical subject headings
- Anemia, Iron-Deficiency, Ventricular Dysfunction, Left, Heart Failure, Iron Deficiencies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sucrosomial ironDietary supplement
Also called SiderAL Forte
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
PlaceboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Sucrosomial iron | Active comparator | Not described Receives: Dietary Supplement: Sucrosomial iron |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in six-minute walk test (6MWT) distance, expressed as meters
Measured: 12 weeks
Difference in Kansan City Cardiomyopathy Questionnaire (KCCQ)-12 overall score
Measured: 12 weeks
Secondary outcomes (28)
Proportion of patients with 15 meters improvement in 6MWT distance (responders)
Measured: 12 weeks
Proportion of patients with 5-point improvement in KCCQ-12 score (responders)
Measured: 12 weeks
Difference in six-minute walk test (6MWT) distance, expressed as meters
Measured: 24 weeks
Difference in Kansan City Cardiomyopathy Questionnaire (KCCQ)-12 overall score
Measured: 24 weeks
Proportion of patients with 15 meters improvement in 6MWT distance (responders)
Measured: 24 weeks
Proportion of patients with 5-point improvement in KCCQ-12 score (responders)
Measured: 24 weeks
Bone metabolism indices
Change in phosphate and FGF-23
Measured: 12 weeks
Bone metabolism indices
Change in phosphate and FGF-23
Measured: 24 weeks
Iron indices
Change in TSAT, ferritin and serum iron
Measured: 12 weeks
Iron indices
Change in TSAT, ferritin and serum iron
Measured: 24 weeks
Oxidative stress
Change in F2-isoprostanes, Soluble NOX2-derived peptide and H2O2
Measured: 12 weeks
Oxidative stress
Change in F2-isoprostanes, Soluble NOX2-derived peptide and H2O2
Measured: 24 weeks
Iron indices 2
change in soluble receptor of transferrin and hepcidin
Measured: 12 weeks
Iron indices 2
change in soluble receptor of transferrin and hepcidin
Measured: 24 weeks
Systolic cardiac function
Change in Left ventricular ejection fraction, %
Measured: 12 weeks
Systolic cardiac function
Change in left ventricular ejection fraction, %
Measured: 24 weeks
NTproBNP
Change in NT-proBNP
Measured: 12 weeks
NTproBNP
Change in NT-proBNP
Measured: 24 weeks
Clinical events
Time to death or to first HF hospitalization
Measured: 12 weeks
Clinical events
Time to death or to first HF hospitalization
Measured: 24 weeks
Left atrial volume
Change in left atrial volume
Measured: 12 weeks
Left ventricular volume
Change in left ventricular end-diastolic volume
Measured: 12 weeks
Left ventricular diastolic function
change in E/e' ratio
Measured: 12 weeks
Echocardiographic estimation of pulmonary pressure
change in systolic pulmonary artery pressure
Measured: 12 weeks
Left atrial volume
Change in left atrial volume
Measured: 24 weeks
Left ventricular diastolic function
change in E/e' ratio
Measured: 24 weeks
Echocardiographic estimation of pulmonary pressure
change in systolic pulmonary artery pressure
Measured: 24 weeks
Left ventricular volume
Change in left ventricular end-diastolic volume
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2024
- Study start14 Mar 2024
- Primary completion14 Mar 2026 (estimated)
- Study completion14 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Raffaele De Caterina
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pisa
- Responsible party
- Sponsor-investigator, Raffaele De Caterina, Azienda Ospedaliero, Universitaria Pisana
- Investigators
- Gabriele Masini, MD PhD, Principal investigator, University of PisaRaffaele De Caterina, MD PhD, Study director, University of Pisa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06270498
- Sponsor's protocol ID
- 24811
- Acronym
- RISE-HF
- Status last verified
- Sep 2025
- First submitted
- 10 Feb 2024
- Last updated
- 1 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT06270498
- Acronym / sponsor ID
- RISE-HF / 24811
- Keywords
- heart failure, iron deficiency, sucrosomial iron
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Raffaele De CaterinaUniversity, hospital or other
- Collaborators
- University of Pisa
- Study start
- 14 Mar 2024 (actual)
- Primary completion
- 14 Mar 2026 (estimated)
- Study completion
- 14 Jun 2026 (estimated)
- First posted
- 21 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sucrosomial iron | Active comparator | Dietary Supplement: Sucrosomial iron |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (23 listed)
- 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 \>100 beats per minute at rest
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sucrosomial ironAlso: SiderAL ForteSucrosomial 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 | Dietary supplement | Sucrosomial iron |
| PlaceboPlacebo 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. | Other | Placebo |
Primary outcome
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
28 secondary outcomes
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
Iron indices 2
Time frame: 12 weeks
Iron indices 2
Time frame: 24 weeks
Systolic cardiac function
Time frame: 12 weeks
Systolic cardiac function
Time frame: 24 weeks
NTproBNP
Time frame: 12 weeks
NTproBNP
Time frame: 24 weeks
Clinical events
Time frame: 12 weeks
Clinical events
Time frame: 24 weeks
Left atrial volume
Time frame: 12 weeks
Left ventricular volume
Time frame: 12 weeks
Left ventricular diastolic function
Time frame: 12 weeks
Echocardiographic estimation of pulmonary pressure
Time frame: 12 weeks
Left atrial volume
Time frame: 24 weeks
Left ventricular diastolic function
Time frame: 24 weeks
Echocardiographic estimation of pulmonary pressure
Time frame: 24 weeks
Left ventricular volume
Time frame: 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Gabriele Masini, MD PhD principal investigator
University of Pisa
Raffaele De Caterina, MD PhD study director
University of Pisa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sucrosomial iron in people with Chronic Heart Failure and Iron-deficiency, run by Raffaele De Caterina at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gabriele Masini, MD PhD (0039 050996712, gabriele.masini@unipi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in six-minute walk test (6MWT) distance, expressed as meters (time frame: 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2025.