Heart Failure With Normal Ejection FractionPhase 3PREFER-HFNCT03833336
Effects of Iron Therapy in Heart Failure With Preserved Ejection Fraction and Iron Deficiency (PREFER-HF)
A Phase 3 study testing Ferric carboxymaltose, Ferroglycine Sulfate and Sucrosomial Iron in people with Heart Failure With Normal Ejection Fraction and Ferropenic Anemia, run by Institut de Recerca Biomèdica de Lleida at 2 sites in Spain.
Trial summary
The purpose of the study is to evaluate whether the administration of iron to patients with heart failure and preserved ejection fraction results in an improvement of symptoms and functional class, in addition to evaluating whether oral iron is equivalent to intravenous iron to achieve this improvement. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Normal Ejection Fraction, Ferropenic Anemia
- What is being tested?
- Ferric carboxymaltose, Ferroglycine Sulfate and Sucrosomial Iron
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 2 sitesSpain
- Study dates
- 23 Aug 2017to 20 Dec 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- Subjects with stable chronic HF (NYHA II/IV functional class) on optimal background therapy (as determined by the investigator) for at least 4 weeks with no dose changes of heart failure drugs during the last 2 weeks (with the exception of diuretics). In general, optimal pharmacological treatment should include an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker and a beta blocker unless contraindicated or not tolerated and diuretic if indicated.
- Left ventricular ejection fraction >45% (value within 3 months of planned date of randomization).
- BNP >100 pg/mL and/or N-terminal-pro-BNP >400 pg/mL at the screening visit.
- Subject must be capable of completing the 6 minute walking test
- Screening serum ferritin <100 ng/mL or 100-300 ng/mL with transferrin saturation <20%.
- At least 18 years of age.
- Before any study-specific procedure, the appropriate written informed consent must be obtained.
Who cannot join
- Subject has known sensitivity to any of the products to be administered during dosing.
- History of acquired iron overload.
- History of erythropoietin-stimulating agent, i.v. iron therapy, and/or blood transfusion in previous 6 weeks prior torandomization.
- Oral iron therapy at doses >100 mg/day in previous 1 week prior to randomization. Note: ongoing use of multivitamins containing iron <75 mg/day is permitted.
- Exercise training programme(s) in the 3 months prior to screening or planned in the next 6 months.
- Known active bacterial infection.
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- Chronic liver disease (including active hepatitis) and/or screening alanine transaminase or aspartate transaminase above three times the upper limit of the normal range.
- Subjects with known hepatitis B surface antigen positivity and/or hepatitis C virus ribonucleic acid positivity.
- Vitamin B12 and/or serum folate deficiency. If deficiency-corrected subject may be rescreened for inclusion.
- Subjects with known seropositivity to human immunodeficiency virus.
- Clinical evidence of current malignancy with exception of basal cell or squamous cell carcinoma of the skin, and cervical intraepithelial neoplasia.
- Currently receiving systemic chemotherapy and/or radiotherapy.
- Renal dialysis (previous, current, or planned within the next 6 months).
- Unstable angina pectoris as judged by the investigator; severe valvular or left ventricular outflow obstruction disease needing intervention; atrial fibrillation/flutter with a mean ventricular response rate at rest >100 beats per minute.
- Acute myocardial infarction or acute coronary syndrome, transient ischemic attack, or stroke within the last 3 months prior to randomization.
- Coronary artery bypass graft, percutaneous intervention (e.g. cardiac, cerebrovascular, and aortic; diagnostic catheters are allowed), or major surgery, including thoracic and cardiac surgery, within the last 3 months prior to randomization.
- Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(ies), or subject is receiving other investigational agent(s).
- Subject of childbearing potential who is pregnant (e.g. positive human chorionic gonadotropin test) or is breastfeeding.
- Subject will not be available for all protocol-specified assessments.
- Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
Trial locations and contacts
2 sites in 1 country.
Spain2 sites
Hospital Universitari Arnau de Vilanova
Lleida, Lleida
Hospital de Manises
Manises, Valencia
About this study
Official title: Effects of Intravenous Iron Therapy With Ferric Carboxymaltose Compared With Oral Iron Therapy in Heart Failure With Preserved Ejection Fraction and Iron Deficiency (PREFER-HF)
The purpose of the study is to evaluate whether the administration of iron to patients with heart failure and preserved ejection fraction results in an improvement of symptoms and functional class, in addition to evaluating whether oral iron is equivalent to intravenous iron to achieve this improvement.
Read the detailed description
Iron deficiency is one of the most prevalent co-morbid conditions in chronic heart failure. In the absence of any iron treatment, it is estimated that up to 50% of patients with heart failure have low levels of available iron. Treatment with intravenous iron improves exercise tolerance , quality of life , and reduces hospitalization in patients with chronic heart failure and reduced ejection fraction. However data on the effect of iron therapy in patients with heart failure with preserved ejection fraction are still lacking. The evidence related to oral iron therapy in HF is limited and no randomized trials compared oral iron vs no iron therapy in the absence of erythropoiesis-stimulating agents.
- Being tested
- Placebo, Ferric carboxymaltose, Ferroglycine Sulfate, Sucrosomial Iron
- Keywords
- heart failure, preserved ejection fraction, ferropenic anemia
- Medical subject headings
- Anemia, Iron-Deficiency, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
The group assigned to placebo will receive an infusion of normal saline solution plus oral lactose capsules identical to oral medication.
Ferric carboxymaltoseDrug
The group assigned to receive intravenous iron will receive intravenous ferric carboxymaltose ajusted by weight and Hb levels according to study protocol plus oral placebo
Ferroglycine SulfateDrug
One group assigned to receive oral iron will receive two 100 mg oral capsule of ferroglycine sulfate plus intravenous placebo (normal saline solution)
Sucrosomial IronDrug
One group assigned to receive oral iron will receive or two oral capsule containing 30 mg of pyrophosphate sucrosomial iron plus intravenous placebo (normal saline solution)
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | normal saline solution plus oral lactose capsules Receives: Other: Placebo |
| Intravenous ferric carboxymaltose | Active comparator | Ferric carboxymaltose 500-1000 mg at 0,6,12,24 weeks ( adjusted by protocol) Receives: Drug: Ferric carboxymaltose |
| Oral iron A: ferroglycine sulfate | Active comparator | oral capsules of ferroglycine sulfate iron until week 24 Receives: Drug: Ferroglycine Sulfate |
| Oral iron B: sucrosomial iron | Active comparator | oral capsules of sucrosomial iron until week 24 Receives: Drug: Sucrosomial Iron |
What is being measured
The primary outcome is the main question the study is designed to answer.
Six minute walking test distance
Change in meters traveled in six minute walking test from baseline to week 24. An increase in distance is related to an improvement in functional capacity.
Measured: 24 weeks
Secondary outcomes (4)
Change in New York Heart Association (NYHA) functional classification
Change in New York Heart Association functional classification (I-IV) from baseline to week 24. A decrease is related to an improvement in functional capacity.
Measured: 24 weeks
Quality of Life assesed by Kansas City Cardiomyopathy Questionnaire
Change in Minnesota Living with Heart Failure questionnaire (0-100) from baseline to week 24. Questionnaire is s a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life.
Measured: 24 weeks
Hospitalizations
Rate of any, HF-related or other cardiovascular hospitalizations.
Measured: 24 weeks
Mortality
All causes and cardiovascular mortality
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 posted7 Feb 2019
- Study start23 Aug 2017
- Primary completion15 Sep 2024
- Study completion20 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Normal Ejection FractionStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut de Recerca Biomèdica de Lleida
- Sponsor type
- University, hospital or other
- Collaborators
- Fundació La Marató de TV3
- Responsible party
- Principal investigator, José Luis Morales Rull, MD, PhD, Institut de Recerca Biomèdica de Lleida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03833336
- Sponsor's protocol ID
- PREFER-HF
- Other IDs
- 2016-003604-31, 2016
- Acronym
- PREFER-HF
- Status last verified
- May 2025
- First submitted
- 5 Feb 2019
- Last updated
- 21 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Intravenous Iron Therapy With Ferric Carboxymaltose Compared With Oral Iron Therapy in Heart Failure With Preserved Ejection Fraction and Iron Deficiency (PREFER-HF)
- ClinicalTrials.gov ID
- NCT03833336
- Acronym / sponsor ID
- PREFER-HF / PREFER-HF
- Keywords
- heart failure, preserved ejection fraction, ferropenic anemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Institut de Recerca Biomèdica de LleidaUniversity, hospital or other
- Collaborators
- Fundació La Marató de TV3
- Study start
- 23 Aug 2017 (actual)
- Primary completion
- 15 Sep 2024 (actual)
- Study completion
- 20 Dec 2024 (actual)
- First posted
- 7 Feb 2019 (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 purpose of the study is to evaluate whether the administration of iron to patients with heart failure and preserved ejection fraction results in an improvement of symptoms and functional class, in addition to evaluating whether oral iron is equivalent to intravenous iron to achieve this improvement.
Detailed description
Iron deficiency is one of the most prevalent co-morbid conditions in chronic heart failure. In the absence of any iron treatment, it is estimated that up to 50% of patients with heart failure have low levels of available iron. Treatment with intravenous iron improves exercise tolerance , quality of life , and reduces hospitalization in patients with chronic heart failure and reduced ejection fraction. However data on the effect of iron therapy in patients with heart failure with preserved ejection fraction are still lacking. The evidence related to oral iron therapy in HF is limited and no randomized trials compared oral iron vs no iron therapy in the absence of erythropoiesis-stimulating agents.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: Placebonormal saline solution plus oral lactose capsules |
| Intravenous ferric carboxymaltose | Active comparator | Drug: Ferric carboxymaltoseFerric carboxymaltose 500-1000 mg at 0,6,12,24 weeks ( adjusted by protocol) |
| Oral iron A: ferroglycine sulfate | Active comparator | Drug: Ferroglycine Sulfateoral capsules of ferroglycine sulfate iron until week 24 |
| Oral iron B: sucrosomial iron | Active comparator | Drug: Sucrosomial Ironoral capsules of sucrosomial iron until week 24 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects with stable chronic HF (NYHA II/IV functional class) on optimal background therapy (as determined by the investigator) for at least 4 weeks with no dose changes of heart failure drugs during the last 2 weeks (with the exception of diuretics). In general, optimal pharmacological treatment should include an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker and a beta blocker unless contraindicated or not tolerated and diuretic if indicated.
- Left ventricular ejection fraction >45% (value within 3 months of planned date of randomization).
- BNP >100 pg/mL and/or N-terminal-pro-BNP >400 pg/mL at the screening visit.
- Subject must be capable of completing the 6 minute walking test
- Screening serum ferritin <100 ng/mL or 100-300 ng/mL with transferrin saturation <20%.
Key exclusion criteria (20 listed)
- Subject has known sensitivity to any of the products to be administered during dosing.
- History of acquired iron overload.
- History of erythropoietin-stimulating agent, i.v. iron therapy, and/or blood transfusion in previous 6 weeks prior torandomization.
- Oral iron therapy at doses >100 mg/day in previous 1 week prior to randomization. Note: ongoing use of multivitamins containing iron <75 mg/day is permitted.
- Exercise training programme(s) in the 3 months prior to screening or planned in the next 6 months.
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 |
|---|---|---|
| PlaceboThe group assigned to placebo will receive an infusion of normal saline solution plus oral lactose capsules identical to oral medication. | Other | Placebo |
| Ferric carboxymaltoseThe group assigned to receive intravenous iron will receive intravenous ferric carboxymaltose ajusted by weight and Hb levels according to study protocol plus oral placebo | Drug | Intravenous ferric carboxymaltose |
| Ferroglycine SulfateOne group assigned to receive oral iron will receive two 100 mg oral capsule of ferroglycine sulfate plus intravenous placebo (normal saline solution) | Drug | Oral iron A: ferroglycine sulfate |
| Sucrosomial IronOne group assigned to receive oral iron will receive or two oral capsule containing 30 mg of pyrophosphate sucrosomial iron plus intravenous placebo (normal saline solution) | Drug | Oral iron B: sucrosomial iron |
Primary outcome
Six minute walking test distance
Time frame: 24 weeks
Change in meters traveled in six minute walking test from baseline to week 24. An increase in distance is related to an improvement in functional capacity.
4 secondary outcomes
Change in New York Heart Association (NYHA) functional classification
Time frame: 24 weeks
Quality of Life assesed by Kansas City Cardiomyopathy Questionnaire
Time frame: 24 weeks
Hospitalizations
Time frame: 24 weeks
Mortality
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2025.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ferric carboxymaltose, Ferroglycine Sulfate and Sucrosomial Iron in people with Heart Failure With Normal Ejection Fraction and Ferropenic Anemia, run by Institut de Recerca Biomèdica de Lleida at 2 sites in Spain.
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 7 inclusion and 20 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: finished, as of the sponsor's last update on 21 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Spain. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Six minute walking test distance (time frame: 24 weeks). 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 21 May 2025.