RecruitingPhase 4NCT06427343

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

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)

Sponsor

China-Japan Friendship Hospital

Enrollment

114 participants

Start Date

Oct 1, 2023

Study Type

INTERVENTIONAL

Conditions

Heart Failure Iron-deficiency

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria8

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.

Exclusion Criteria16

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.
Participation in another intervention study involving a drug or device within the past 90 days.

Interventions

DRUGHigh-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.

DRUGLow-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.