The Effects of Low-Dose Versus High-Dose Intravenous IRON Therapy With Ferric DerisomaltOSE in Patients With Chronic Heart Failure and Iron Deficiency

NCT ID: NCT06427343

Last Updated: 2025-02-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

114 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-10-01

Study Completion Date

2026-12-21

Brief Summary

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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

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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

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Heart Failure Iron Deficiency

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Drug: Ferric Derisomaltose
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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High dose

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.

Group Type EXPERIMENTAL

High-dose ferric derisomaltose

Intervention Type DRUG

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

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.

Group Type ACTIVE_COMPARATOR

Low-dose ferric derisomaltose

Intervention Type DRUG

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.

Interventions

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High-dose ferric derisomaltose

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.

Intervention Type DRUG

Low-dose ferric derisomaltose

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.

Intervention Type DRUG

Other Intervention Names

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More intensive target Less intensive target

Eligibility Criteria

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Inclusion Criteria

1. Age \>18 years.
2. Left ventricular ejection fraction (LVEF) \<50% within 2 years prior to planned randomization (assessed by echocardiography or MRI).
3. New York Heart Association (NYHA) class II \~ III.
4. 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.
5. 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).
6. Serum ferritin \<100 ng/mL or serum ferritin 100-300 ng/mL and TSAT \<20%.
7. Able and willing to perform a CPET at the time of randomization.
8. Able and willing to provide informed consent.

Exclusion Criteria

1. Hemoglobin \<9.0 g/dL or Hemoglobin \>15.0 g/dL.
2. Renal dialysis or MDRD/CKD-EPI estimated glomerular filtration rate (eGFR) \<15 ml/min/1.73m2.
3. Body weight \<35 kg.
4. Heart failure was secondary to valvular diseases or congenital heart diseases.
5. History of acquired iron overload; known hemochromatosis or first relatives with hemochromatosis.
6. Known hypersensitivity to ferric derisomaltose or other IV iron product.
7. 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.
8. 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.
9. Acute myocardial infarction, acute coronary syndrome, transient ischemic attack, or stroke within 3 months prior to randomization.
10. Revascularization therapy (coronary artery bypass grafting, percutaneous intervention, or major surgery) within 3 months prior to randomization; or planning cardiac surgery or revascularization.
11. Already receiving erythropoietin, IV or oral iron therapy, and blood transfusion in previous 30 days prior to randomization.
12. Use of concurrent immunosuppressive therapy
13. 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.
14. Investigator considers a possible alternative diagnosis to account for the patient's HF symptoms: severe obesity, primary pulmonary hypertension, or chronic obstructive pulmonary disease.
15. Pregnancy or breast feeding.
16. Participation in another intervention study involving a drug or device within the past 90 days.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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China-Japan Friendship Hospital

OTHER

Sponsor Role lead

Responsible Party

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Jingyi Ren

Professor of medicine(Cardiology), Deputy Director of the Cardiology Department and Director of the Heart Failure Center

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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China-Japan Friendship Hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Jingyi Ren

Role: CONTACT

18600195099

Lina Su

Role: CONTACT

18801230212

Facility Contacts

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Lina Su

Role: primary

18801230212

Other Identifiers

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2023-ZF-62

Identifier Type: -

Identifier Source: org_study_id

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