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

Официальное название

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)

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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.

Первичные конечные точки

• Change in peak VO2 (ml/min/kg） [Срок оценки: Baseline to Week 52]

Вторичные конечные точки (12)

• Change in VO2 at ventilatory threshold (ml/min） [Срок оценки: Baseline to Week 52]
• Change in heart rate at peak exercise (bpm) [Срок оценки: Baseline to Week 52]
• Change in peak respiratory exchange ratio [Срок оценки: Baseline to Week 52]
• Change in 6-minute walking distance (m) [Срок оценки: Baseline to Week 26 and Week 52]
• Change in myocardial iron content by cardiac magnetic resonance imaging T2 star [Срок оценки: Baseline to Week 52]
• Change in skeletal muscle iron content by magnetic resonance imaging T2 star [Срок оценки: Baseline to Week 52]
• Change in the clinical summary score by Kansas City Cardiomyopathy Questionnaire (KCCQ) [Срок оценки: Baseline to Week 52]
• Change in the EQ-5D-5L questionnaire indexed value [Срок оценки: Baseline to Week 52]
• Change in cognitive function score by Mini-Mental State Examination (MMSE) [Срок оценки: Baseline to Week 52]
• Change in concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP, pg/mL) [Срок оценки: Baseline to Week 52]
• Change in left ventricular ejection fraction (LVEF, %) [Срок оценки: Baseline to Week 52]
• Change in left ventricular global longitudinal stress (LVGLS, %) [Срок оценки: Baseline to Week 52]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• China-Japan Friendship Hospital — Пекин

Идентификаторы

NCT: NCT06427343 · 2023-ZF-62

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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