Heart FailurePhase 4IRONDOSENCT06427343
The Effects of Low-Dose Versus High-Dose Intravenous IRON Therapy With Ferric DerisomaltOSE in Patients With Chronic Heart Failure and Iron Deficiency
A Phase 4 study testing High-dose ferric derisomaltose and Low-dose ferric derisomaltose in people with Heart Failure and Iron Deficiency, run by China-Japan Friendship Hospital at 1 site in China.
Trial summary
This study will address whether intravenous (IV) iron repletion with a more intensive target will provide greater benefits in improving exercise capacity for patients with chronic heart failure and iron deficiency. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Iron Deficiency
- What is being tested?
- High-dose ferric derisomaltose and Low-dose ferric derisomaltose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 1 siteChina
- Study dates
- 1 Oct 2023to 1 Aug 2027
- 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
- Age >18 years.
- Left ventricular ejection fraction (LVEF) <50% within 2 years prior to planned randomization (assessed by echocardiography or MRI).
- New York Heart Association (NYHA) class II ~ III.
- Either hospitalization for HF within 6 months prior to planned randomization or elevated plasma levels of natriuretic peptides within 3 months of randomization. a. For patients in sinus rhythm: NT- proBNP >300 pg/mL or BNP >100 pg/mL. b. For patients in atrial fibrillation: NT-proBNP >600 pg/mL or BNP >200 pg/mL.
- Subjects with stable CHF (NYHA II/III 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).
- Serum ferritin <100 ng/mL or serum ferritin 100-300 ng/mL and TSAT <20%.
- Able and willing to perform a CPET at the time of randomization.
- Able and willing to provide informed consent.
Who cannot join
- Hemoglobin <9.0 g/dL or Hemoglobin >15.0 g/dL.
- Renal dialysis or MDRD/CKD-EPI estimated glomerular filtration rate (eGFR) <15 ml/min/1.73m2.
- Body weight <35 kg.
- Heart failure was secondary to valvular diseases or congenital heart diseases.
- History of acquired iron overload; known hemochromatosis or first relatives with hemochromatosis.
- Known hypersensitivity to ferric derisomaltose or other IV iron product.
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- Known active infection (defined as currently treated with oral or intravenous antibiotics), bleeding (gastrointestinal hemorrhagia, menorrhagia, history of peptic ulcer with no evidence of healing or inflammatory bowel disease), malignancy, and hemolytic anemia.
- History of chronic liver disease and/or alanine transaminase (ALT) or aspartate transaminase (AST) >3 times the upper limit of the normal range; myelodysplastic disorder; and known HIV/AIDS disease.
- Acute myocardial infarction, acute coronary syndrome, transient ischemic attack, or stroke within 3 months prior to randomization.
- Revascularization therapy (coronary artery bypass grafting, percutaneous intervention, or major surgery) within 3 months prior to randomization; or planning cardiac surgery or revascularization.
- Already receiving erythropoietin, IV or oral iron therapy, and blood transfusion in previous 30 days prior to randomization.
- Use of concurrent immunosuppressive therapy
- Any of the following diseases that hinders exercise testing: severe musculoskeletal disease, unstable angina, obstructive cardiomyopathy, severe uncorrected valvular disease, or uncontrolled slow or rapid arrhythmia (mean ventricular rate >100 beats/min at rest), or uncontrolled hypertension with blood pressure >160/100 mm Hg.
- Investigator considers a possible alternative diagnosis to account for the patient's HF symptoms: severe obesity, primary pulmonary hypertension, or chronic obstructive pulmonary disease.
- Pregnancy or breast feeding.
- Participation in another intervention study involving a drug or device within the past 90 days.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
China-Japan Friendship Hospital
Beijing, Beijing Municipality, 100044
Lina Su, 18801230212, sln920722@163.com
Jingyi Ren
About this study
Official title: The Effects of Low-dose Versus High-dose Intravenous Iron Therapy With Ferric Derisomaltose in Patients With Chronic Heart Failure and Iron Deficiency: a Randomized, Open-label, Blind Endpoint Trial (IRONDOSE)
This study will address whether intravenous (IV) iron repletion with a more intensive target will provide greater benefits in improving exercise capacity for patients with chronic heart failure and iron deficiency. One group of participants will receive a high-dose IV iron regimen with a more intensive target, and the other group will receive a low-dose IV iron regimen with a less intensive target.
Read the detailed description
Iron deficiency is a common and important comorbidity in heart failure. Randomized controlled trials have consistently demonstrated a beneficial effect of IV iron on exercise capacity and quality of life in iron-deficient patients with HF and reduced ejection fraction. However, these randomized controlled trials exhibit striking heterogeneity in targeting levels for maintenance strategies of IV iron repletion. Some studies (FERRIC-HF, FAIR-HF) withheld intravenous iron in cases of ferritin >800 ng/mL, hemoglobin >16.0 g/dL, or transferrin saturation (TSAT) >50%, while other studies (HEART-FID, IRONMAN) focused on targeting levels that are simply above the definition of iron deficiency. Additionally, the PIVOTAL trial showed that high-dose IV iron decreased recurrent heart failure events in patients undergoing hemodialysis compared to a lower-dose regimen. Whether functional outcomes differ between those on lower versus higher iron repletion targets among patients with heart failure remains unknown. This study will help us address this question.
This is an investigator-initiated, prospective, randomized, open-label blind endpoint study to assess the effects of high-dose IV iron repletion compared to a low-dose IV iron repletion on 12-month change in peak oxygen uptake (VO2) for patients with chronic heart failure and concomitant iron deficiency.
Patients with chronic heart failure and iron deficiency will be enrolled and randomized in a 1:1 ratio to receive a high-dose IV iron regimen and a low-dose IV iron regimen. After the initial iron repletion, ferritin concentration and TSAT were measured every three months and the results used to determine the dose of ferric derisomaltose during the follow-up period. In the high dose group, iron dosing will repeat as long as the serum ferritin was not >700ng/mL, or if TSAT was not >40%. Patients in the low dose group will receive repeat iron dosing if ferritin <100 ng/mL, or if ferritin 100-300 ng/mL and TSAT <20%, in line with criteria for iron deficiency in current guidelines.
- Conditions
- Heart Failure, Iron Deficiency
- Being tested
- High-dose ferric derisomaltose, Low-dose ferric derisomaltose
- Keywords
- IRONDOSE
- Medical subject headings
- Heart Failure, Iron Deficiencies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-dose ferric derisomaltoseDrug
Also called More intensive target
After baseline assessment, participants will be randomized in a 1:1 ratio to receive a high-dose IV iron regimen and a low-dose IV iron regimen. After the initial iron repletion, ferritin concentration and TSAT were measured every three months and the results used to determine the dose of ferric derisomaltose during follow-up.
In the high-dose group, participants will receive repeat iron dosing as long as the serum ferritin was not >700 ng/mL, or if TSAT was not >40% during follow-up.
Low-dose ferric derisomaltoseDrug
Also called Less intensive target
In the low-dose group, participants will receive repeat iron dosing if ferritin <100 ng/mL or if ferritin 100-300 ng/mL and TSAT >20% during follow-up.
| Study group | Role | What they receive |
|---|---|---|
| High dose | Experimental | Participants randomized to this arm will receive repeat iron dosing as long as the serum ferritin was not >700 ng/mL, or if TSAT was not >40% during follow-up.
Iron to be administered as ferric derisomaltose. Ferric derisomaltose will be administered according to the dosing schedule determined by the patient's body weight and hemoglobin value.
Infused over a minimum of 15 mins for doses up to and including 1000mg, and a minimum of 30 mins for doses >1000mg. Receives: Drug: High-dose ferric derisomaltose |
| Low dose | Active comparator | Participants randomized to this arm will receive repeat iron dosing if ferritin <100 ng/mL or if ferritin 100-300 ng/mL and TSAT <20% during follow-up.
Iron to be administered as ferric derisomaltose in analogy to high-dose arm. Receives: Drug: Low-dose ferric derisomaltose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in peak VO2 (ml/min/kg）
Peak VO2 measured by a maximal effort Cardiopulmonary Exercise Test (CPET)
Measured: Baseline to Week 52
Secondary outcomes (13)
Change in VO2 at ventilatory threshold (ml/min）
Measured by CPET
Measured: Baseline to Week 52
Change in heart rate at peak exercise (bpm)
Measured by CPET
Measured: Baseline to Week 52
Change in peak respiratory exchange ratio
Measured by CPET
Measured: Baseline to Week 52
Change in 6-minute walking distance (m)
Measured: Baseline to Week 26 and Week 52
Change in myocardial iron content by cardiac magnetic resonance imaging T2 star
Measured by cardiac magnetic resonance imaging
Measured: Baseline to Week 52
Change in skeletal muscle iron content by magnetic resonance imaging T2 star
Measured by skeletal muscle magnetic resonance imaging
Measured: Baseline to Week 52
Change in the clinical summary score by Kansas City Cardiomyopathy Questionnaire (KCCQ)
The KCCQ is a validated instrument for self-assessment of quality of life and health status in heart failure patients. The clinical summary score, which is derived from the physical limitations and heart failure symptoms domains of the KCCQ is a valid measure for assessing the patient's health aspects that may be influenced by CV medications. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
Measured: Baseline to Week 52
Change in the EQ-5D-5L questionnaire indexed value
EQ-5D-5L: European Quality of Life-5 Dimensions-5 Levels The EQ 5D questionnaire consists of a health descriptive system for participants to self-classify and rate their health status on the day of administration. The descriptive system includes 5 items/dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression, which are coded from 1 (best state) to 5 (worst state).
Measured: Baseline to Week 52
Change in cognitive function score by Mini-Mental State Examination (MMSE)
The MMSE is a cognitive test. The score is ranged from 0-30 (units of a scale). 30 points is the better outcome. The investigators will assess the change in the score.
Measured: Baseline to Week 52
Change in concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP, pg/mL)
Tested in blood samples
Measured: Baseline to Week 52
Change in left ventricular ejection fraction (LVEF, %)
Assessed by echocardiography
Measured: Baseline to Week 52
Change in left ventricular global longitudinal stress (LVGLS, %)
Assessed by echocardiography
Measured: Baseline to Week 52
Mortality and heart failure-related hospitalization rates
Effects on mortality and HF-related hospitalization rates in patients with heart failure.
Measured: Up to 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2024
- Study start1 Oct 2023
- Primary completion1 Aug 2027 (estimated)
- Study completion1 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by China-Japan Friendship HospitalThe sponsor's other registered studies.
- 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
- Model description
- Drug: Ferric Derisomaltose
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 114 participants (estimated)
Sponsor and investigators
- Lead sponsor
- China-Japan Friendship Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jingyi Ren, China-Japan Friendship Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06427343
- Sponsor's protocol ID
- 2023-ZF-62
- Acronym
- IRONDOSE
- Status last verified
- Nov 2026
- First submitted
- 19 May 2024
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Low-dose Versus High-dose Intravenous Iron Therapy With Ferric Derisomaltose in Patients With Chronic Heart Failure and Iron Deficiency: a Randomized, Open-label, Blind Endpoint Trial (IRONDOSE)
- ClinicalTrials.gov ID
- NCT06427343
- Acronym / sponsor ID
- IRONDOSE / 2023-ZF-62
- Conditions
- Heart Failure, Iron Deficiency
- Keywords
- IRONDOSE
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 114 participants (estimated)
- Lead sponsor
- China-Japan Friendship HospitalUniversity, hospital or other
- Study start
- 1 Oct 2023 (actual)
- Primary completion
- 1 Aug 2027 (estimated)
- Study completion
- 1 Aug 2027 (estimated)
- First posted
- 23 May 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.
This study will address whether intravenous (IV) iron repletion with a more intensive target will provide greater benefits in improving exercise capacity for patients with chronic heart failure and iron deficiency. One group of participants will receive a high-dose IV iron regimen with a more intensive target, and the other group will receive a low-dose IV iron regimen with a less intensive target.
Detailed description
Iron deficiency is a common and important comorbidity in heart failure. Randomized controlled trials have consistently demonstrated a beneficial effect of IV iron on exercise capacity and quality of life in iron-deficient patients with HF and reduced ejection fraction. However, these randomized controlled trials exhibit striking heterogeneity in targeting levels for maintenance strategies of IV iron repletion. Some studies (FERRIC-HF, FAIR-HF) withheld intravenous iron in cases of ferritin >800 ng/mL, hemoglobin >16.0 g/dL, or transferrin saturation (TSAT) >50%, while other studies (HEART-FID, IRONMAN) focused on targeting levels that are simply above the definition of iron deficiency. Additionally, the PIVOTAL trial showed that high-dose IV iron decreased recurrent heart failure events in patients undergoing hemodialysis compared to a lower-dose regimen. Whether functional outcomes differ between those on lower versus higher iron repletion targets among patients with heart failure remains unknown. This study will help us address this question.
This is an investigator-initiated, prospective, randomized, open-label blind endpoint study to assess the effects of high-dose IV iron repletion compared to a low-dose IV iron repletion on 12-month change in peak oxygen uptake (VO2) for patients with chronic heart failure and concomitant iron deficiency.
Patients with chronic heart failure and iron deficiency will be enrolled and randomized in a 1:1 ratio to receive a high-dose IV iron regimen and a low-dose IV iron regimen. After the initial iron repletion, ferritin concentration and TSAT were measured every three months and the results used to determine the dose of ferric derisomaltose during the follow-up period. In the high dose group, iron dosing will repeat as long as the serum ferritin was not >700ng/mL, or if TSAT was not >40%. Patients in the low dose group will receive repeat iron dosing if ferritin <100 ng/mL, or if ferritin 100-300 ng/mL and TSAT <20%, in line with criteria for iron deficiency in current guidelines.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Drug: Ferric Derisomaltose
| Arm | Type | Receives |
|---|---|---|
| High dose | Experimental | Drug: High-dose ferric derisomaltoseParticipants randomized to this arm will receive repeat iron dosing as long as the serum ferritin was not >700 ng/mL, or if TSAT was not >40% during follow-up. Iron to be administered as ferric derisomaltose. Ferric derisomaltose will be administered according to the dosing schedule determined by the patient's body weight and hemoglobin value. Infused over a minimum of 15 mins for doses up to and including 1000mg, and a minimum of 30 mins for doses >1000mg. |
| Low dose | Active comparator | Drug: Low-dose ferric derisomaltoseParticipants randomized to this arm will receive repeat iron dosing if ferritin <100 ng/mL or if ferritin 100-300 ng/mL and TSAT <20% during follow-up. Iron to be administered as ferric derisomaltose in analogy to high-dose arm. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age >18 years.
- Left ventricular ejection fraction (LVEF) <50% within 2 years prior to planned randomization (assessed by echocardiography or MRI).
- New York Heart Association (NYHA) class II ~ III.
- Either hospitalization for HF within 6 months prior to planned randomization or elevated plasma levels of natriuretic peptides within 3 months of randomization. a. For patients in sinus rhythm: NT- proBNP >300 pg/mL or BNP >100 pg/mL. b. For patients in atrial fibrillation: NT-proBNP >600 pg/mL or BNP >200 pg/mL.
- Subjects with stable CHF (NYHA II/III 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).
Key exclusion criteria (16 listed)
- Hemoglobin <9.0 g/dL or Hemoglobin >15.0 g/dL.
- Renal dialysis or MDRD/CKD-EPI estimated glomerular filtration rate (eGFR) <15 ml/min/1.73m2.
- Body weight <35 kg.
- Heart failure was secondary to valvular diseases or congenital heart diseases.
- History of acquired iron overload; known hemochromatosis or first relatives with hemochromatosis.
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 |
|---|---|---|
| High-dose ferric derisomaltoseAlso: More intensive targetAfter baseline assessment, participants will be randomized in a 1:1 ratio to receive a high-dose IV iron regimen and a low-dose IV iron regimen. After the initial iron repletion, ferritin concentration and TSAT were measured every three months and the results used to determine the dose of ferric derisomaltose during follow-up. In the high-dose group, participants will receive repeat iron dosing as long as the serum ferritin was not >700 ng/mL, or if TSAT was not >40% during follow-up. | Drug | High dose |
| Low-dose ferric derisomaltoseAlso: Less intensive targetIn the low-dose group, participants will receive repeat iron dosing if ferritin <100 ng/mL or if ferritin 100-300 ng/mL and TSAT >20% during follow-up. | Drug | Low dose |
Primary outcome
Change in peak VO2 (ml/min/kg）
Time frame: Baseline to Week 52
Peak VO2 measured by a maximal effort Cardiopulmonary Exercise Test (CPET)
13 secondary outcomes
Change in VO2 at ventilatory threshold (ml/min）
Time frame: Baseline to Week 52
Change in heart rate at peak exercise (bpm)
Time frame: Baseline to Week 52
Change in peak respiratory exchange ratio
Time frame: Baseline to Week 52
Change in 6-minute walking distance (m)
Time frame: Baseline to Week 26 and Week 52
Change in myocardial iron content by cardiac magnetic resonance imaging T2 star
Time frame: Baseline to Week 52
Change in skeletal muscle iron content by magnetic resonance imaging T2 star
Time frame: Baseline to Week 52
Change in the clinical summary score by Kansas City Cardiomyopathy Questionnaire (KCCQ)
Time frame: Baseline to Week 52
Change in the EQ-5D-5L questionnaire indexed value
Time frame: Baseline to Week 52
Change in cognitive function score by Mini-Mental State Examination (MMSE)
Time frame: Baseline to Week 52
Change in concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP, pg/mL)
Time frame: Baseline to Week 52
Change in left ventricular ejection fraction (LVEF, %)
Time frame: Baseline to Week 52
Change in left ventricular global longitudinal stress (LVGLS, %)
Time frame: Baseline to Week 52
Mortality and heart failure-related hospitalization rates
Time frame: Up to 52 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 5 Nov 2026.
- 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.
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 High-dose ferric derisomaltose and Low-dose ferric derisomaltose in people with Heart Failure and Iron Deficiency, run by China-Japan Friendship Hospital at 1 site in China.
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 8 inclusion and 16 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 5 Nov 2026. 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 China. 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. 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 Jingyi Ren (18600195099, renjingyi1213@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in peak VO2 (ml/min/kg） (time frame: Baseline to Week 52). 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 5 Nov 2026.