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

NCT06427343 | Recruiting Phase 4 DMC

• 1 other identifier: 2023-ZF-62
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Heart Failure; Iron Deficiency

Keywords

IRONDOSE

Outcome Measures

Primary Outcomes (1)

• Change in peak VO2 (ml/min/kg）

  Peak VO2 measured by a maximal effort Cardiopulmonary Exercise Test (CPET)

  Baseline to Week 52

Secondary Outcomes (13)

• Change in VO2 at ventilatory threshold (ml/min）

  Baseline to Week 52

• Change in heart rate at peak exercise (bpm)

  Baseline to Week 52

• Change in peak respiratory exchange ratio

  Baseline to Week 52

• Change in 6-minute walking distance (m)

  Baseline to Week 26 and Week 52

• Change in myocardial iron content by cardiac magnetic resonance imaging T2 star

  Baseline to Week 52

Study Arms (2)

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.

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.

Drug: Low-dose ferric derisomaltose

Interventions

High-dose ferric derisomaltose 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.

Also known as: More intensive target

High dose

Low-dose ferric derisomaltose 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.

Also known as: Less intensive target

Low dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• China-Japan Friendship Hospital: lead

Study Sites (1)

China-Japan Friendship Hospital

Beijing, Beijing Municipality, 100044, China

RECRUITING

MeSH Terms

Conditions

Heart Failure; Iron Deficiencies

Interventions

ferric derisomaltose

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Jingyi Ren

CONTACT

18600195099; renjingyi1213@hotmail.com

Lina Su

CONTACT

18801230212; sln920722@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of medicine(Cardiology), Deputy Director of the Cardiology Department and Director of the Heart Failure Center

Model Details: Drug: Ferric Derisomaltose

Study Record Dates

• First Submitted: May 19, 2024
• First Posted: May 23, 2024
• Study Start: October 1, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 21, 2026
• Last Updated: February 19, 2025

Record last verified: 2025-02

Locations

CN (1)